Evaluation of CRAG screening with enhanced antifungal therapy for asymptomatic CRAG-positive persons

对无症状 CRAG 阳性者进行强化抗真菌治疗的 CRAG 筛查评估

基本信息

批准号：
10341089
负责人：
Radha Rajasingham
金额：
$ 16.21万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-02-05 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10341089
关键词：
AIDS-Related Opportunistic Infections Acquired Immunodeficiency Syndrome Adherence Adult Africa South of the Sahara Amphotericin Amphotericin B Antifungal Agents Antifungal Therapy Antigens Biometry Blood CD4 Lymphocyte Count Caring Cause of Death Cells Cessation of life Clinical Clinical Research Clinical Trials Communicable Diseases Cost Effectiveness Analysis Counseling Country Cryptococcal Meningitis Cryptococcus Custom Data Decision Analysis Diagnostic Disease Dose Evaluation Expert Opinion Failure Fluconazole Future Goals Guidelines HIV HIV therapy Infection Inferior International K-Series Research Career Programs Liposomes Medicine Meningitis Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Minnesota Morbidity - disease rate Patients Persons Plasma Policies Prevention Public Health Recommendation Research Research Methodology Research Personnel Resource Allocation Resources South Africa Symptoms Testing Therapeutic Time Training Translating Uganda Universities Validation advanced disease aggressive therapy antiretroviral therapy base career clinical care cost effective cost effective intervention cost effectiveness cost-effectiveness evaluation cost-effectiveness ratio effective intervention effective therapy effectiveness evaluation experience improved improved outcome incremental cost-effectiveness individualized medicine innovation interest lateral flow assay models and simulation mortality multidisciplinary novel point of care prevent professor randomized trial screening screening guidelines skills standard of care therapy outcome treatment guidelines treatment strategy

项目摘要

Dr. Rajasingham is an Assistant Professor in the Division of Infectious Diseases & International Medicine at the University of Minnesota. Her long-term goal is to become an independent investigator with expertise in evaluating the effectiveness and cost-effectiveness of innovative diagnostics and therapeutics related to the prevention and management of AIDS-related opportunistic infections. She is particularly interested in using cost-effectiveness analysis alongside clinical trials, in order to translate effective interventions into policy. Training: This K23 award will provide the mentored clinical research experience and didactic training in decision analysis and simulation modeling necessary to establish her independent research career. With the mentorship of an interdisciplinary team with expertise in decision analysis, biostatistics, and HIV international clinical trials, she will: 1) acquire advanced training in decision analysis and simulation modeling, 2) acquire expertise in HIV international clinical research methodology, and 3) develop multidisciplinary collaborative and networking skills. Research: Cryptococcus is a leading cause of AIDS-related morbidity and mortality worldwide. Cryptococcal antigen (CRAG) can be detected in the blood weeks to months prior to the onset of meningitis and is an independent predictor of mortality. A public health strategy to reduce mortality is to screen for CRAG in the plasma of people entering HIV care with a CD4 count <100 cells/mcL. Those who are asymptomatic CRAG+ can be treated preemptively with fluconazole antifungal therapy to prevent meningitis or death while receiving HIV therapy. Despite the survival benefit associated with this WHO-recommended CRAG screening and treatment strategy, ~30% of asymptomatic CRAG+ persons die despite standard of care treatment with fluconazole. Those with high CRAG titers (>1:160) are 3 times more likely to die than are those with low CRAG titers (<1:80) in blood. I hypothesize that customized antifungal therapy based on CRAG titers will improve survival, whereby patients with high titers (>1:160) require more aggressive antifungal therapy. The overall objective of this proposal is to identify a more clinically effective yet economically feasible treatment strategy for asymptomatic CRAG+ persons. The aims of this proposal are to: 1) determine if enhanced antifungal therapy improves 6-month survival for asymptomatic persons with high CRAG titers; 2) determine the cost-effectiveness of enhanced antifungal therapy for HIV-infected CRAG+ persons, stratified by CRAG titer; and 3) validate a novel semi-quantitative CRAG lateral flow assay to rapidly detect high CRAG titers (>1:160). The proposed study seeks to improve the international standard of clinical care for HIV-infected persons with advanced disease, and to generate evidence that will inform international HIV care guidelines. The findings and the training in decision analysis that Dr. Rajasingham will obtain will inform future proposals to evaluate cost-effective strategies to reduce AIDS-related deaths across sub-Saharan Africa.

Rajasingham博士是在传染病和国际医学系的助理教授明尼苏达大学。她的长期目标是成为具有专业知识的独立调查员评估创新诊断和治疗剂的有效性和成本效益预防和管理与艾滋病相关的机会感染。她对使用特别感兴趣成本效益分析以及临床试验以及将有效的干预措施转化为政策。培训：该K23奖将提供指导的临床研究经验和教学培训决策分析和仿真建模为建立她的独立研究生涯所必需的。与具有决策分析，生物统计学和艾滋病毒国际的专业知识的跨学科团队的指导临床试验，她将：1）在决策分析和模拟建模中获得高级培训，2）获取艾滋病毒国际临床研究方法的专业知识，以及3）发展多学科合作和网络技能。研究：隐球菌是全球与艾滋病有关的发病率和死亡率的主要原因。在脑膜炎发作之前的几周到几个月中，可以在血液中检测到隐球菌抗原（CRAG）并且是死亡率的独立预测指标。降低死亡率的公共卫生策略是筛选碎屑在患有CD4计数<100个细胞/mcl的艾滋病毒护理的人的血浆中。那些无症状的人 crag+可以通过氟康唑抗真菌疗法进行预先治疗，以防止脑膜炎或死亡接受艾滋病毒疗法。尽管与该名人推荐的crag筛选有关的生存益处和治疗策略，尽管有标准的护理治疗，约有30％的无症状crag+人死亡氟康唑。那些具有较高的岩壁滴度（> 1：160）的人死亡的可能性是低crag的可能性的3倍血液中的滴度（<1:80）。我假设基于岩壁滴度的定制抗真菌疗法将改善生存期，高滴度（> 1：160）的患者需要更具侵略性的抗真菌治疗。该提案的总体目的是确定一个更有效但经济上可行的更有效的无症状crag+人的治疗策略。该提议的目的是：1）确定是否是否增强的抗真菌疗法可改善高crag滴度的无症状患者的6个月生存期； 2）确定艾滋病毒感染的crag+人的增强抗真菌疗法的成本效益，由 crag滴度； 3）验证一种新型的半定量crag横向流程测定以快速检测高crag 滴度（> 1：160）。拟议的研究旨在提高艾滋病毒感染的国际临床护理标准患有晚期疾病的人，并产生可以为国际艾滋病毒护理指南提供信息的证据。 Rajasingham博士将获得的发现和决策分析的培训将为以后的建议提供信息评估撒哈拉以南非洲的成本效益策略，以减少与艾滋病相关的死亡。

项目成果

期刊论文数量（43）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cryptococcosis in pregnancy and the postpartum period: Case series and systematic review with recommendations for management.

妊娠期和产后期的隐球菌病：病例系列和系统评价以及管理建议。

DOI：
10.1093/mmy/myz084
发表时间：
2020
期刊：
Medical mycology
影响因子：
2.9
作者：
Pastick,KatelynA;Nalintya,Elizabeth;Tugume,Lillian;Ssebambulidde,Kenneth;Stephens,Nicole;Evans,EmilyE;Ndyetukira,JaneFrances;Nuwagira,Edwin;Skipper,Caleb;Muzoora,Conrad;Meya,DavidB;Rhein,Joshua;Boulware,DavidR;Rajasingham,R
通讯作者：
Rajasingham,R

Correction to Lancet Infect Dis 2022; published online Aug 29. https://doi.org/10.1016/S1473-3099(22)00499-6.

DOI：
10.1016/s1473-3099(22)00597-7
发表时间：
2023-01
期刊：
LANCET INFECTIOUS DISEASES
影响因子：
56.3
作者：
通讯作者：

An updated systematic review of HIV-associated cryptococcal meningitis treatment strategies.

HIV 相关隐球菌性脑膜炎治疗策略的最新系统评价。

DOI：
10.1111/hiv.13412
发表时间：
2023
期刊：
HIV medicine
影响因子：
3
作者：
Shapiro,AdrienneE;Tenforde,MarkW;Chiller,TomM;Ford,Nathan;Rajasingham,Radha
通讯作者：
Rajasingham,Radha

Effect of Coronavirus Disease 2019 Lockdowns on Identification of Advanced Human Immunodeficiency Virus Disease in Outpatient Clinics in Uganda.

2019 年冠状病毒病封锁对乌干达门诊晚期人类免疫缺陷病毒病鉴定的影响。

DOI：
10.1093/cid/ciad087
发表时间：
2023
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
0
作者：
Nalintya,Elizabeth;Sekar,Preethiya;Kavuma,Paul;Kigozi,Joanita;Ssuna,Martin;Kirumira,Paul;Naluyima,Rose;Namuli,Teopista;Musa,FredTurya;Skipper,CalebP;Hullsiek,KathyHuppler;Ellis,Jayne;Boulware,DavidR;Meya,DavidB;Rajasingham
通讯作者：
Rajasingham

Sterile Cerebrospinal Fluid Culture at Cryptococcal Meningitis Diagnosis Is Associated with High Mortality.