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.

项目摘要/摘要 非洲艾滋病毒的孕妇与疟疾的共同感染率很高，并且性传播 感染（性传播感染）导致不利的母亲和出生结果，包括死产，早产， 艾滋病毒的低出生体重和垂直传播。预防疟疾可改善产妇和围产期 结果，但目前的方案受到新兴耐药性和与药物的严重相互作用的限制 用于HIV患者。通过双重预防的新型药物方案的鉴定 怀孕中的疟疾和可治愈的细菌性传播疾病将是改善预后的重要创新 在这个脆弱的妇女和婴儿中。为了解决这个紧迫的问题，此K23应用程序 描述了申请人的背景和经验，乔迪·A·狄奥尼·奥多姆（Jodie A. Dionne-Odom）及其收购计划 成为预防的独立，领先科学家所必需的知识和培训 撒哈拉以南非洲的HIV感染孕妇的共同感染。她的K23培训目标 要：（1）在资源有限的设置中设计和进行临床试验的设计和行为（2）增益 流行病学和生物统计学的高级培训，包括围产期流行病学，药物安全监测 和感染建模技术； （3）获取测量疟疾和STI终点的技能以及（4）增益 在执行人类受试者研究以及授予和手稿准备方面的其他培训。见面 这些目标是与跨学科团队共同制定的全面培训计划 是成熟的高级研究专家的导师和顾问。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以及 会议。配备了此培训，Dionne-Odom博士将进行研究以测试是否新颖 三甲氧苄啶 - 磺胺甲恶唑（TMP）和阿奇霉素（AZ）的预防性疗法（AZ）是优越的 对于当前的标准疟疾预防（TMP）以及它是否具有减少STI的额外好处 流行率。在特定的目标1中，将执行II期随机对照试验以测试的功效 与HIV感染的孕妇中的TMP相比，与TMP相比，预防治疗方案的组合组合。这 一级疗效结果将减少分娩时周围疟疾负荷。在特定目标中 2，将测量35周妊娠（或分娩）后可治疗细菌性传播感染的患病率，并 在两臂之间进行比较。在特定的目标3中，胎儿/新生儿安全和依从性/耐受性 将确定组合方案。该II阶段试验的数据将用于支持R-01 III期 撒哈拉以南非洲的多中心随机对照试验。从该奖项获得的培训 结合该项目的结果，将有助于狄恩·奥多姆（Dionne-Odom）博士成功过渡到 研究独立性和成功。