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

• 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
• 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

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博士是传染病和国际医学部的助理教授 明尼苏达大学。她的长期目标是成为一名独立调查员，在 评估与以下方面相关的创新诊断和治疗的有效性和成本效益 预防和管理与艾滋病相关的机会性感染。她尤其对使用 结合临床试验进行成本效益分析，以便将有效的干预措施转化为政策。 培训：这项K23奖项将提供临床研究指导经验和教学培训 决策分析和仿真建模是她建立独立研究生涯所必需的。与 指导具有决策分析、生物统计学和艾滋病毒国际专业知识的跨学科团队 临床试验，她将：1)获得决策分析和仿真建模方面的高级培训，2)获得 在艾滋病毒国际临床研究方法方面的专业知识，以及3)发展多学科合作和 网络技能。 研究：隐球菌是全球艾滋病相关发病率和死亡率的主要原因。 隐球菌抗原(CRAG)可在脑膜炎发作前几周至几个月在血液中检测到 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查岩壁 在进入HIV治疗的人的血浆中，CD4计数为100个细胞/毫升。那些没有症状的人 CRIG+可先发制人地使用氟康唑抗真菌治疗，以防止脑膜炎或死亡 接受艾滋病毒治疗。尽管与WHO推荐的岩壁筛查相关的生存益处 和治疗策略，约30%的无症状ARG+患者死亡，尽管接受了标准的护理治疗 氟康唑。那些岩石滴度高(<gt；1：160)的人死亡的可能性是那些低岩石的人的3倍。 血液中的效价(1：80)。我推测，基于ROG滴度的定制化抗真菌疗法将有所改善 生存，因此高滴度(<gt；1：160)的患者需要更积极的抗真菌治疗。 这项建议的总体目标是确定在临床上更有效但在经济上可行的 对无症状岩壁+患者的治疗策略。这项提案的目的是：1)确定是否 增强的抗真菌治疗提高了高滴度无症状患者的6个月存活率； 确定针对HIV感染的CRAG+患者的强化抗真菌治疗的成本-效果，按 岩壁滴度；3)验证一种新的半定量岩壁侧向流动分析方法，以快速检测高岩层 效价(&gt；1：160)。这项拟议的研究旨在提高艾滋病毒感染者临床护理的国际标准 对患有晚期疾病的人进行监测，并提供证据，为国际艾滋病毒护理指南提供参考。 Rajasingham博士将获得的发现和决策分析方面的培训将为未来的提案提供参考 评估在整个撒哈拉以南非洲减少艾滋病相关死亡的成本效益战略。

项目成果

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

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

• DOI: 10.3390/jof9010046
• 发表时间: 2022-12-28
• 期刊: Journal of fungi (Basel, Switzerland)

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
• 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

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

Safety of Hydroxychloroquine Among Outpatient Clinical Trial Participants for COVID-19.

• DOI: 10.1093/ofid/ofaa500
• 发表时间: 2020-11
• 期刊: Open forum infectious diseases
• 影响因子: 4.2
• 作者: Lofgren SM;Nicol MR;Bangdiwala AS;Pastick KA;Okafor EC;Skipper CP;Pullen MF;Engen NW;Abassi M;Williams DA;Nascene AA;Axelrod ML;Lother SA;MacKenzie LJ;Drobot G;Marten N;Cheng MP;Zarychanski R;Schwartz IS;Silverman M;Chagla Z;Kelly LE;McDonald EG;Lee TC;Hullsiek KH;Boulware DR;Rajasingham R
• 通讯作者: Rajasingham R