Investigating interactions between efavirenz-based antiretroviral therapy and contraceptive implants

研究基于依非韦伦的抗逆转录病毒疗法与植入式避孕药之间的相互作用

• 批准号: 9178400
• 负责人: Rena Chiman Patel
• 金额: $ 14.63万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9178400
• 关键词: Investigating; interactions; between; efavirenz; based

 DESCRIPTION (provided by applicant): The overall goal of the proposed mentored career development award is to support Dr. Rena Patel's research training to develop as an independent, mixed methods researcher in HIV and women's health. Dr. Patel is currently an infectious diseases fellow at the University of California, San Francisco. Conducting the proposed studies in this application will facilitate her training goals of gaining a background in pharmacology, advancing her skills in epidemiology/biostatistics and qualitative research methods, and formalizing her experiences in implementation sciences. The proposal builds on the unique skills that she already has in the social sciences, qualitative research, and epidemiology while leveraging UCSF's world-class mentors, researchers, and facilities to ensure her success in becoming an independent investigator. The research objective of this proposal is to determine if interactions between efavirenz and contraceptive implants lead to contraceptive failures (i.e. unintended pregnancies). Unintended pregnancies among HIV-positive women impact HIV and maternal morbidity and vertical transmission of HIV. Optimizing contraception to avoid unintended pregnancies is imperative. Some pharmacokinetic data regarding drug-drug interactions between efavirenz and hormonal contraception have raised concerns for increased contraceptive failures. However, critical gaps exist in the literature and current HIV treatment guidelines with regard to concomitant use of efavirenz-based antiretroviral therapy (ART), now recommended as first-line ART in resource-limited settings, and contraceptive implants. In order to address the issue of potential interactions between efavirenz and implants comprehensively, we aim to conduct three distinct studies in western Kenya. For Aim 1, we will determine if implant etonogestrel concentrations decrease following initiation of efavirenz-based ART. For Aim 2, we will compare contraceptive failure or pregnancy rates among women using implants on efavirenz- vs. non-efavirenz based ART in a large clinic-based Kenyan cohort. Lastly, for Aim 3, we will determine how HIV-positive women, their partners, and providers reach decisions regarding concomitant ART and contraception initiation and choices, how potential data on interactions between ART and contraception would influence their choices, and to assess acceptability of alternative ART and/or contraceptive strategies. We hypothesize that implant etonogestrel concentrations will decrease following efavirenz-based ART initiation and pregnancy rates will be higher in implant users on efavirenz vs. non-efavirenz-based ART. The above aims will be among the first to comprehensively address the questions surrounding interactions between efavirenz-based ART and implants, and by the completion of this award, Dr. Patel will be in an excellent position to submit an R01 that furthers the research agenda in HIV and reproductive health.

 描述（由申请人提供）：拟议的指导职业发展奖的总体目标是支持 Rena Patel 博士的研究培训，使其成为艾滋病毒和妇女健康领域的独立、混合方法研究员。Patel 博士目前是一名传染病研究员。在加利福尼亚大学旧金山分校进行本申请中提出的研究将有助于她获得药理学背景、提高流行病学/生物统计学和定性研究方法方面的技能以及将她的实施经验形式化的培训目标。该提案建立在她在社会科学、定性研究和流行病学方面已有的独特技能的基础上，同时利用加州大学旧金山分校的世界一流的导师、研究人员和设施，以确保她成功成为一名独立研究者。该提案的目的是确定依非韦伦和埋植剂之间的相互作用是否会导致艾滋病毒阳性妇女的避孕失败（即意外怀孕），从而影响艾滋病毒和孕​​产妇发病率。优化避孕措施以避免意外怀孕势在必行。有关依非韦伦和激素避孕之间药物相互作用的一些药代动力学数据引起了人们对避孕失败率增加的担忧。然而，文献和当前的艾滋病毒治疗指南在这方面存在重大差距。同时使用基于依非韦伦的抗逆转录病毒治疗（ART）（目前推荐在资源有限的环境中作为一线 ART）和避孕植入物。为了全面解决依非韦伦和植入物之间的潜在相互作用问题，我们的目标是在肯尼亚西部进行三项不同的研究，对于目标 1，我们将确定植入物依托孕烯浓度在开始基于依非韦伦的 ART 后是否会降低。在肯尼亚大型临床队列中比较使用基于依非韦伦和非依非韦伦的 ART 植入物的妇女的避孕失败或怀孕率。 最后，对于目标 3，我们将确定艾滋病毒呈阳性的妇女、她们的伴侣和提供者如何就同时进行抗逆转录病毒治疗和避孕措施的启动和选择做出决定，有关抗逆转录病毒治疗和避孕之间相互作用的潜在数据将如何影响她们的选择，并评估替代抗逆转录病毒治疗和/或避孕措施的可接受性我们的目标是，在开始基于依非韦伦的 ART 后，植入物依托孕烯浓度将会降低，并且使用依非韦伦的植入物使用者的妊娠率将高于非基于依非韦伦的 ART。成为第一批全面解决基于依非韦伦的 ART 与植入物之间相互作用问题的人之一，在完成该奖项后，Patel 博士将处于有利地位，可以提交 R01，进一步推进 艾滋病毒和生殖健康的研究议程。