A Novel Regimen to Prevent Malaria and STIs in Pregnant Women with HIV

预防艾滋病毒孕妇疟疾和性传播感染的新疗法

基本信息

批准号：
9766109
负责人：
Jodie Ann Dionne
金额：
$ 16.74万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-23 至 2021-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9766109
关键词：
Address Adherence Africa Africa South of the Sahara African Anemia Antibiotics Antigens Antimalarials Area Award Azithromycin Biometry Birth Blood CD4 Lymphocyte Count Cameroon Central Africa Cessation of life Chlamydia trachomatis Clinical Sciences Conduct Clinical Trials Country Data Development Directly Observed Therapy Disease Dose Epidemiology Falciparum Malaria Fetal Growth Retardation Goals HIV Human Subject Research Immunity Infant Infection Infection prevention Intervention Knowledge Late pregnancy Low Birth Weight Infant Low Prevalence Macrolide Antibiotics Malaria Malaria prevention Manuscripts Measures Mentors Microscopy Modeling Monitor Neisseria gonorrhoeae Neonatal Newborn Infant Nucleic Acid Amplification Tests Outcome Parasitemia Parasites Participant Patients Perinatal Perinatal Epidemiology Perinatal Infection Perinatal mortality demographics Peripheral Pharmaceutical Preparations Phase Pregnancy Pregnant Women Premature Birth Preparation Prevalence Prevention Prophylactic treatment Pyrimethamine-Sulfadoxine Questionnaires Randomized Randomized Controlled Trials Regimen Reporting Research Research Project Grants Resistance Resources Risk Risk Factors Safety Scientist Sepsis Serious Adverse Event Sexually Transmitted Diseases Streptococcus Group B Swab Syphilis Syphilis Serodiagnosis Techniques Testing Training Translational Research Treponema pallidum Trimethoprim-Sulfamethoxazole Vagina Vertical Disease Transmission Visit Vulnerable Populations Woman Women&apos s Group World Health Organization adverse pregnancy outcome arm co-infection cost density design efficacy testing experience fetal follow-up hands-on learning improved improved outcome innovation malaria infection maternal morbidity medication compliance medication safety neonatal morbidity novel novel therapeutics open label parity pathogen pathogenic bacteria perinatal outcomes phase II trial prenatal testing prevent prophylactic randomized trial skills standard of care stillbirth success symposium transmission process treatment arm treatment as usual usual care arm young woman

项目摘要

Project Summary/Abstract Pregnant women with HIV in Africa have high rates of coinfection with malaria and sexually transmitted infections (STIs) that contribute to adverse maternal and birth outcomes including stillbirth, preterm delivery, low birth weight and vertical transmission of HIV. Malaria prophylaxis improves maternal and perinatal outcomes but current regimens are limited by emerging resistance and serious interactions with medications that are used in patients with HIV. The identification of a novel drug regimen with dual prevention for both malaria and curable bacterial STIs in pregnancy would be an important innovation toward improved outcomes in this vulnerable group of women and infants. To address this pressing problem, this K23 application describes the background and experience of the applicant, Jodie A. Dionne-Odom, MD and her plan to acquire the knowledge and training necessary to become an independent, leading scientist in the prevention and treatment of coinfections in HIV-infected pregnant women in sub-Saharan Africa. Her K23 training objectives are to: (1) develop expertise in the design and conduct of clinical trials in resource-limited settings (2) gain advanced training in epidemiology and biostatistics including perinatal epidemiology, drug safety monitoring and infection modeling techniques; (3) acquire skills in measuring malaria and STI endpoints and (4) gain additional training in performing human subjects research and grant and manuscript preparation. To meet these objectives, a comprehensive training plan has been developed in concert with an interdisciplinary team of mentors and consultants who are established senior research experts. The plan includes hands-on learning, coursework leading to an MSPH in Clinical and Translational Science and supplemental short courses and conferences. Equipped with this training, Dr. Dionne-Odom will conduct research to test whether a novel combination prophylactic regimen of trimethoprim-sulfamethoxazole (TMPS) and azithromycin (AZ) is superior to the current standard malaria prophylaxis (TMPS) and whether it has the added benefit of reducing STI prevalence. In Specific Aim 1, a phase II randomized controlled trial will be performed to test the efficacy of the combination prophylaxis regimen TMPS-AZ compared to TMPS in HIV-infected pregnant women. The primary efficacy outcome will be a decrease in the peripheral malaria parasite load at delivery. In Specific Aim 2, the prevalence of treatable bacterial STIs after 35 weeks gestation (or delivery) will be measured and compared between both arms. In Specific Aim 3, the fetal/neonatal safety and adherence/tolerability of the combination regimen will be determined. Data from this phase II trial will be used to support an R-01 phase III multicenter randomized controlled trial in sub-Saharan Africa. The training acquired from this award in combination with results from this project will facilitate the successful transition of Dr. Dionne-Odom to research independence and success.

项目概要/摘要非洲感染艾滋病毒的孕妇同时感染疟疾和性传播疾病的比例很高导致不良孕产妇和分娩结果的感染（性传播感染），包括死产、早产、低出生体重和艾滋病毒垂直传播。疟疾预防可改善孕产妇和围产期症状但目前的治疗方案受到新出现的耐药性和与药物的严重相互作用的限制用于艾滋病毒患者。确定一种具有双重预防作用的新药物治疗方案怀孕期间的疟疾和可治愈的细菌性传播感染将是改善结局的重要创新在妇女和婴儿这一弱势群体中。为了解决这个紧迫的问题，这个K23应用程序描述了申请人 Jodie A. Dionne-Odom 医学博士的背景和经验以及她收购的计划成为预防和预防方面的独立领先科学家所需的知识和培训撒哈拉以南非洲地区艾滋病毒感染孕妇合并感染的治疗。她的 K23 培训目标目标是： (1) 发展在资源有限的环境中设计和进行临床试验的专业知识 (2) 获得流行病学和生物统计学高级培训，包括围产期流行病学、药物安全监测和感染建模技术； (3) 获得测量疟疾和性传播感染终点的技能以及 (4) 收益进行人类受试者研究以及拨款和手稿准备方面的额外培训。见面为了实现这些目标，我们与跨学科团队合作制定了全面的培训计划导师和顾问都是资深的研究专家。该计划包括实践学习、获得临床和转化科学硕士学位的课程以及补充短期课程和会议。接受此培训后，迪翁-奥多姆博士将进行研究，以测试一部小说是否甲氧苄啶-磺胺甲恶唑 (TMPS) 和阿奇霉素 (AZ) 的联合预防方案效果更佳当前的标准疟疾预防 (TMPS) 以及它是否具有减少性传播感染的额外益处流行率。在具体目标 1 中，将进行 II 期随机对照试验来测试以下药物的功效： HIV 感染孕妇的联合预防方案 TMPS-AZ 与 TMPS 的比较。这主要疗效结果是分娩时外周疟原虫数量的减少。特定目标 2、妊娠 35 周（或分娩）后，将测量可治疗的细菌性 STI 的患病率，并两臂之间进行比较。在具体目标 3 中，胎儿/新生儿的安全性和依从性/耐受性将确定联合方案。该 II 期试验的数据将用于支持 R-01 III 期试验撒哈拉以南非洲地区的多中心随机对照试验。通过该奖项获得的培训结合该项目的成果将有助于 Dionne-Odom 博士成功过渡到研究的独立性和成功。