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

• 批准号: 9270984
• 负责人: Jodie Ann Dionne
• 金额: $ 16.83万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 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/9270984
• 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; Learning; Life; Low Birth Weight Infant; 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; World Health Organization; abstracting; adverse pregnancy outcome; arm; co-infection; cost; density; design; efficacy testing; experience; fetal; follow-up; improved; improved outcome; innovation; malaria infection; maternal morbidity; medication compliance; meetings; neonatal morbidity; novel; novel therapeutics; open label; parity; pathogen; perinatal outcomes; phase II trial; prenatal; prevent; prophylactic; randomized trial; screening; skills; standard of care; stillbirth; success; symposium; treatment as usual; young woman

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.

项目总结/摘要 非洲感染艾滋病毒的孕妇合并感染疟疾和性传播疾病的比率很高 导致不良孕产妇和分娩结果的性传播感染，包括死胎、早产， 低出生体重和艾滋病毒的垂直传播。疟疾预防改善孕产妇和围产期 但目前的治疗方案受到新出现的耐药性和与药物严重相互作用的限制 用于艾滋病患者。确定一种双重预防的新型药物方案， 疟疾和可治愈的细菌性性传播感染将是改善结果的重要创新 在这个弱势群体的妇女和婴儿。为了解决这个紧迫的问题，K23应用程序 描述了申请人Jodie A的背景和经验。Dionne-Odom，MD和她的收购计划 知识和必要的培训，成为一个独立的，领先的科学家在预防和 治疗撒哈拉以南非洲感染艾滋病毒的孕妇的合并感染。K23训练目标 目的是：（1）在资源有限的环境中开发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 （3）掌握衡量疟疾和性传播感染终点的技能;（4）获得 在进行人类受试者研究以及赠款和手稿准备方面的额外培训。满足 为了实现这些目标，与一个跨学科小组合作制定了一项全面的培训计划。 导师和顾问谁是建立高级研究专家。该计划包括动手学习， 课程导致临床和转化科学和补充短期课程的MSPH， 两会有了这种训练，迪昂-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）联合预防性用药方案是一种较好的上级方案 与目前的疟疾预防标准（TMPS）相比，它是否具有减少性传播感染的额外好处 普遍性。在具体目标1中，将进行II期随机对照试验，以测试 联合预防方案TMPS-AZ与TMPS在HIV感染孕妇中的比较。的 主要功效结果将是分娩时外周疟疾寄生虫负荷的减少。具体目标 2.将测量35周妊娠（或分娩）后可治疗的细菌性STI的患病率， 对比一下两个手臂。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。 多中心随机对照试验在撒哈拉以南非洲。从该奖项获得的培训， 结合该项目的结果将有助于Dionne-Odom博士成功过渡到 研究的独立性和成功。