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.

摘要声明 国际研究科学家发展奖为理想的概念化机会 支持过渡到候选人的独立性，互联，儿科和儿科感染率 疾病与专家照顾艾滋病毒和结核病儿童和成人（TB）。候选人的 长期目标是成为一名独立的研究者，产生急需的证据，以告知儿童艾滋病毒 和结核病政策和实践。候选人总部位于Eswatini，将在贝勒（Baylor）工作 国际小儿艾滋病倡议（Bipai）诊所网络，位于莱索托，博茨瓦纳，马拉维，马拉维， 坦桑尼亚和乌干达实施这项跨国研究并完成了既定目标。 拟议的研究将指导针对儿童的差异化服务提供以及 患有艾滋病毒（CALHIV）的青少年，患有不良艾滋病毒和艾滋病毒相关的结核病的风险高和低风险。 AIM 1将为Calhiv预测死亡风险12个月而得出并验证死亡率临床预测工具 在抗逆转录病毒疗法的倡议之后。该工具将通过回顾性数据得出和验证 跨越比帕网络。该提案的AIM 2将开发用于病毒非抑制的临床预测工具 研究入学率12个月，使用前瞻性收集的临床数据并考虑其他 心理社会变量，描述了影响抗逆转录病毒疗法依从性的无数因素。目标3意志 还利用比帕网络的强度回顾性确定结核病的发病率和死亡率 与根据根据不同的Isoniazid预防疗法（IPT）策略相关的CALHIV 在Bipai网络中不断发展的国家准则。迫切需要此数据，i）告知基于证据的数据 在接受抗逆转录病毒疗法的儿童中实施IPT，ii）设计新的研究 较短的结核病预防治疗方案。 与所描述的研究相辅相成，候选人将参加数据科学课程，数据 管理，流行病学和临床信息，最终以流行病学的硕士学位达到最终。更远， 候选人将受益于一个由强大的精通团队的直接监督和指导，这将由 Mandalakas博士和Chiao博士（联合促进导师）。曼达卡斯博士拥有超过二十年的经验 在全球儿童健康研究中指导年轻的物理科学家，Chiao博士是国际 公认的艾滋病毒相关恶性肿瘤流行病学专家。 Lukhele博士（LMIC心理和高管 贝勒儿童基金会 - 埃斯瓦蒂尼（Eswatini）的董事拥有丰富的实施公共卫生的经验 Eswatini的研究。 Kirchner博士（Co-Incertor）将监督该提案中进行的统计分析， Skinner博士（Co-Incertor）将指导定性方法，Maldonado博士（Co-Incertor）将提供技术 专业知识从致力于小儿艾滋病毒流行病学的职业中收集到。

项目成果

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

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

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

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

Vikela Ekhaya: A Novel, Community-based, Tuberculosis Contact Management Program in a High Burden Setting.

• DOI: 10.1093/cid/ciab652
• 发表时间: 2022-05-03
• 期刊: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America