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

项目摘要/摘要 非洲携带艾滋病毒的孕妇与疟疾和性传播疾病的混合感染率很高 导致不良母婴结局的感染(STI)，包括死产、早产、 低出生体重和艾滋病毒的垂直传播。预防疟疾可改善孕产妇和围产儿 结果，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 用于艾滋病患者的药物。一种新的双重预防用药方案的确定 孕期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 在这一脆弱的妇女和婴儿群体中。为了解决这个紧迫的问题，这款K23应用程序 描述申请者Jodie A.Dionne-Odon医学博士的背景和经验，以及她的收购计划 成为一名独立的、领先的预防和预防科学家所需的知识和培训 撒哈拉以南非洲艾滋病毒感染孕妇合并感染的治疗。她的K23培训目标 是：(1)在资源有限的情况下发展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方面的高级培训，包括围产期流行病学、药物安全监测 和感染建模技术；(3)掌握测量疟疾和性传播感染终点的技能；(4)获得 在进行人体研究、赠款和手稿准备方面的额外培训。相遇 为了实现这些目标，与一个跨学科团队共同制定了一项全面的培训计划 由资深研究专家组成的导师和顾问组成。该计划包括实践学习， 取得临床和转化学硕士学位的课程和补充的短期课程和 会议。配备了这种培训，迪翁-奥多姆博士将进行研究，以测试一部小说 甲氧苄氨嘧啶-磺胺甲恶唑(TMPS)和阿奇霉素(AZ)联合预防方案效果较好 目前的标准疟疾预防措施(TMPS)，以及它是否具有减少STI的额外好处 流行率。在具体目标1中，将进行第二阶段随机对照试验，以测试 联合预防方案TMPS-AZ与TMPS在HIV感染孕妇中的比较。这个 主要疗效结果将是在分娩时减少外围疟疾寄生虫载量。以特定的目标 2.将在妊娠(或分娩)35周后测量可治疗的细菌性传播感染的患病率，并 两只手臂之间的对比。在具体目标3中，胎儿/新生儿的安全性和依从性/耐受性 联合治疗方案将会确定。来自第二阶段试验的数据将用于支持R-01第三阶段 撒哈拉以南非洲的多中心随机对照试验。年从该奖项获得的培训 与该项目的结果相结合，将有助于迪翁-奥多姆博士成功地过渡到 研究的独立性和成功性。

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.