Developing Clinical Prediction Tools to Define Strategies for Differentiated Service Delivery in Children and Adolescents Living with HIV in sub-Saharan Africa.

开发临床预测工具，以确定为撒哈拉以南非洲地区艾滋病毒感染儿童和青少年提供差异化​​服务的策略。

• 批准号: 10678965
• 负责人: Alexander William Kay
• 金额: $ 13.37万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-18 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10678965
• 关键词: 5 year old; AIDS related cancer; Acquired Immunodeficiency Syndrome; Adherence; Adolescent; Adult; Africa South of the Sahara; Age; Alcohol consumption; Area; Award; Biometry; Botswana; Caring; Cessation of life; Child; Child Care; Child Health; Childhood; Clinic; Clinical; Clinical Data; Clinical Informatics; Clinical Research; Communicable Diseases; Complement; Country; Data; Data Science; Data Set; Derivation procedure; Development; Disease; Drug usage; Enrollment; Epidemic; Epidemiology; Foundations; Future; Goals; Guidelines; HIV; HIV Seropositivity; HIV/TB; Health Services Accessibility; Health system; Healthcare; Immunosuppression; Incidence; International; Internist; Intervention; Knowledge; Laboratories; Lesotho; Malawi; Master of Science; Measures; Mental Depression; Mentored Research Scientist Development Award; Mentors; Mentorship; Modeling; Morbidity - disease rate; Opportunistic Infections; Outcome; Patient Care; Patient-Focused Outcomes; Patients; Physicians; Policies; Population; Positioning Attribute; Preventive therapy; Prospective Studies; Psychosocial Factor; Public Health; Qualitative Methods; Regimen; Research; Research Personnel; Resource-limited setting; Resources; Risk; Risk Estimate; Risk Factors; Risk Reduction; Scientist; Statistical Data Interpretation; Subgroup; Supervision; Surveys; Tanzania; Technical Expertise; Testing; Tuberculosis; Uganda; Validation; Viral; Work; World Health Organization; adverse outcome; age group; antiretroviral therapy; career; clinical implementation; clinical predictors; cohort; comorbidity; data management; design; evidence base; experience; follow-up; health literacy; high risk; improved outcome; isoniazid; low and middle-income countries; mortality; mortality risk; pediatric human immunodeficiency virus; pediatrician; predictive tools; prospective; psychosocial; public health research; research study; risk prediction; risk stratification; screening; service delivery; skills; social stigma; therapy adherence; tool

SUMMARY STATEMENT The International Research Scientist Development Award affords an ideal mentorship opportunity to support the transition to independence of the candidate, an internist, pediatrician and pediatric infectious diseases physician with expertise caring for children and adults with HIV and tuberculosis (TB). The candidate’s long-term goal is to become an independent investigator, generating much needed evidence to inform child HIV and TB policy and practice. The candidate is based full-time in Eswatini and will work across the Baylor International Pediatric AIDS Initiative (BIPAI) network of clinics in Eswatini, Lesotho, Botswana, Malawi, Tanzania and Uganda to implement this multinational research study and accomplish the stated aims. The proposed research will guide implementation of differentiated service delivery for children and adolescents living with HIV (CALHIV) at both high and low risk of adverse HIV and HIV associated TB outcomes. Aim 1 will derive and validate a mortality clinical prediction tool for CALHIV to predict the risk of death 12 months after the initiation of antiretroviral therapy. This tool will be derived and validated using retrospective data from across the BIPAI network. Aim 2 of the proposal will develop a clinical prediction tool for viral non-suppression 12 months from study enrollment using prospectively collected clinical data and considering additional psychosocial variables, describing the myriad of factors impacting antiretroviral therapy adherence. Aim 3 will also harness the strength of the BIPAI network to retrospectively determine TB incidence and mortality rates in CALHIV associated with the different isoniazid preventive therapy (IPT) strategies implemented according to evolving national guidelines across the BIPAI network. This data is urgently needed to i) inform evidence-based implementation of IPT in children receiving antiretroviral therapy, and ii) design prospective studies of new shorter-course tuberculosis preventive therapy regimens. Complementing the described research, the candidate will take courses in data science, data management, epidemiology, and clinical informatics, culminating in a master’s degree in epidemiology. Further, the candidate will benefit from direct supervision and guidance from a strong mentorship team that will be led by Dr. Mandalakas and Dr. Chiao (co-primary mentors). Dr. Mandalakas has over two decades of experience mentoring young physician scientists in global child health research and Dr. Chiao is an internationally recognized expert in the epidemiology of HIV associated malignancies. Dr. Lukhele (LMIC mentor and Executive Director at the Baylor Children’s Foundation-Eswatini) has extensive experience implementing public health research in Eswatini. Dr. Kirchner (co-mentor) will supervise the statistical analysis employed in this proposal, Dr. Skinner (co-mentor) will guide qualitative methods, and Dr. Maldonado (co-mentor) will provide technical expertise gathered from a career devoted to pediatric HIV epidemiology.

简要说明 国际研究科学家发展奖提供了一个理想的导师机会， 支持过渡到独立的候选人，内科医生，儿科医生和儿科感染 拥有专门知识的疾病医生，负责照顾患有艾滋病毒和结核病的儿童和成人。候选人的 长期目标是成为一名独立的调查员，为儿童艾滋病毒提供急需的证据 以及结核病政策和实践。候选人全职工作在斯威士兰，并将在贝勒工作 在斯威士兰、莱索托、博茨瓦纳、马拉维、 坦桑尼亚和乌干达执行这项多国研究，实现既定目标。 拟议的研究将指导为儿童提供差别化服务的实施， 艾滋病毒感染者和艾滋病毒相关结核病后果的高风险和低风险青少年。 目的1将推导并验证一种CALHIV的死亡率临床预测工具，以预测12个月内的死亡风险 在开始抗逆转录病毒治疗后。该工具将使用以下数据进行推导和验证： 在BIPAI网络上。该提案的目标2将开发一种用于病毒非抑制的临床预测工具 使用前瞻性收集的临床数据并考虑其他因素，研究入组后12个月 社会心理变量，描述了影响抗逆转录病毒治疗依从性的众多因素。目标3将 还利用BIPAI网络的优势，回顾性地确定结核病发病率和死亡率， CALHIV与根据以下实施的不同异烟肼预防性治疗（IPT）策略相关 在BIPAI网络中制定国家指导方针。这些数据是迫切需要的，i）告知基于证据的 在接受抗逆转录病毒治疗儿童中实施IPT，以及ii）设计新的 短期结核病预防治疗方案。 作为对所述研究的补充，候选人将参加数据科学，数据 管理学、流行病学和临床信息学，最终获得流行病学硕士学位。此外，本发明还 候选人将受益于由以下人员领导的强大导师团队的直接监督和指导 博士Mandalakas和Dr. Chiao（共同主要导师）。曼达拉卡斯博士有二十多年的经验 在全球儿童健康研究中指导年轻的医生科学家，焦博士是一位国际 HIV相关恶性肿瘤流行病学方面的公认专家。Lukhele博士（LMIC导师和执行官 贝勒儿童基金会-埃斯瓦蒂尼主任）在实施公共卫生方面有着丰富的经验 在斯威士兰的研究。Kirchner博士（共同导师）将监督本提案中使用的统计分析， 博士Skinner（共同导师）将指导定性方法，马尔多纳多博士（共同导师）将提供技术 从致力于儿科艾滋病流行病学的职业生涯中收集的专业知识。

项目成果

Transition to Dolutegravir Is Associated With an Increase in the Rate of Body Mass Index Change in a Cohort of Virally Suppressed Adolescents.

• DOI: 10.1093/cid/ciaa1652
• 发表时间: 2021-08-02
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
• 作者: Thivalapill N;Simelane T;Mthethwa N;Dlamini S;Lukhele B;Okello V;Kirchner HL;Mandalakas AM;Kay AW
• 通讯作者: Kay AW

Xpert MTB/RIF Ultra assay for tuberculosis disease and rifampicin resistance in children.

• DOI: 10.1002/14651858.cd013359.pub3
• 发表时间: 2022-09-06
• 期刊: COCHRANE DATABASE OF SYSTEMATIC REVIEWS
• 影响因子: 8.4
• 作者: Kay, Alexander W.;Ness, Tara;Verkuijl, Sabine E.;Viney, Kerri;Brands, Annemieke;Masini, Tiziana;Fernandez, Lucia Gonzalez;Eisenhut, Michael;Detjen, Anne K.;Mandalakas, Anna M.;Steingart, Karen R.;Takwoingi, Yemisi
• 通讯作者: Takwoingi, Yemisi

Landscape of TB Infection and Prevention among People Living with HIV.

• DOI: 10.3390/pathogens11121552
• 发表时间: 2022-12-16
• 期刊: Pathogens (Basel, Switzerland)
• 作者: Vasiliu A;Abelman R;Kherabi Y;Iswari Saktiawati AM;Kay A
• 通讯作者: Kay A

Making the Case for All-Oral, Shorter Regimens for Children with Drug-Resistant Tuberculosis.

• DOI: 10.1164/rccm.202304-0670vp
• 发表时间: 2023-07-15
• 期刊: American journal of respiratory and critical care medicine
• 影响因子: 24.7

Baseline assessment of pharmacovigilance activities in four sub-Saharan African countries: a perspective on tuberculosis.

• DOI: 10.1186/s12913-021-07043-6
• 发表时间: 2021-10-08
• 期刊: BMC health services research
• 影响因子: 2.8
• 作者: Tiemersma EW;Ali I;Alemu A;Avong YK;Duga A;Elagbaje C;Isah A;Kay A;Mmbaga BT;Mmari E;Mwamwitwa K;Nhlabatsi S;Sintayehu K;Arefayne A;Teferi M;Cobelens F;Härmark L
• 通讯作者: Härmark L