Investigating interactions between efavirenz-based antiretroviral therapy and contraceptive implants

 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雷纳帕特尔博士的研究培训，以发展成为一个独立的，混合方法的艾滋病毒和妇女健康研究人员。Patel博士目前是加州大学旧金山分校弗朗西斯科的传染病研究员。在本申请中进行拟议的研究将有助于她获得药理学背景的培训目标，提高她在流行病学/生物统计学和定性研究方法方面的技能，并使她在实施科学方面的经验正规化。该提案建立在她在社会科学，定性研究和流行病学方面已经拥有的独特技能的基础上，同时利用UCSF世界一流的导师，研究人员和设施，以确保她成功成为独立调查员。 本提案的研究目的是确定依法韦仑与避孕植入剂之间的相互作用是否会导致避孕失败（即意外妊娠）。艾滋病毒抗体阳性妇女的意外怀孕影响艾滋病毒和孕产妇发病率以及艾滋病毒的垂直传播。优化避孕措施以避免意外怀孕势在必行。一些关于依法韦仑和激素避孕药之间药物相互作用的药代动力学数据引起了人们对避孕失败增加的担忧。然而，在文献和目前的艾滋病毒治疗指南中，关于同时使用以依法韦仑为基础的抗逆转录病毒治疗（ART）和避孕植入剂方面存在重大差距，目前建议在资源有限的情况下将其作为一线ART。 为了全面解决依法韦仑和植入物之间的潜在相互作用的问题，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，我们将确定是否植入依托孕烯浓度降低后，开始以依法韦仑为基础的ART。对于目标2，我们将比较避孕失败或妊娠率的妇女使用植入依法韦仑与非依法韦仑为基础的ART在一个大型的诊所为基础的肯尼亚队列。最后，对于目标3，我们将确定艾滋病毒阳性的妇女，他们的合作伙伴，和供应商达成关于伴随ART和避孕的启动和选择的决定，ART和避孕之间的相互作用的潜在数据将如何影响他们的选择，并评估替代ART和/或避孕策略的可接受性。我们假设植入依托孕烯浓度将降低后，依法韦仑为基础的ART开始和怀孕率将更高的植入用户依法韦仑与非依法韦仑为基础的ART。上述目标将是第一个全面解决的问题，围绕依法韦仑为基础的ART和植入物之间的相互作用，并通过完成这一奖项，Patel博士将处于一个很好的位置，提交一份R 01， 艾滋病毒和生殖健康研究议程。

 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.