Investigating interactions between efavirenz-based antiretroviral therapy and contraceptive implants

 描述(由申请者提供)：拟议的导师职业发展奖的总体目标是支持Rena Patel博士的研究培训，以发展成为艾滋病毒和妇女健康方面的独立、混合方法研究员。帕特尔博士目前是加州大学旧金山分校的传染病研究员。在这项申请中进行拟议的研究将有助于实现她的培训目标，即获得药理学背景，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，并将她在实施科学方面的经验正规化。这项提议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，同时利用加州大学旧金山分校世界级的导师、研究人员和设施来确保她成功地成为一名独立的调查员。这项提议的研究目标是确定Eefavirenz和避孕药植入物之间的相互作用是否会导致避孕失败(即意外怀孕)。艾滋病毒阳性妇女的意外怀孕影响艾滋病毒和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是当务之急。一些关于药物间相互作用的药代动力学数据已经引起了人们对避孕失败增加的关注。然而，文献和当前的艾滋病毒治疗指南在同时使用基于efavirenz的抗逆转录病毒疗法(ART)和避孕植入物方面存在严重差距，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Eefavirenz和植入物之间的潜在相互作用问题，我们计划在肯尼亚西部进行三项不同的研究。对于目标1，我们将确定在开始基于efavirenz的ART后，植入物中的依托诺孕酮浓度是否降低。对于目标2，我们将在肯尼亚的一个大型临床队列中比较使用efavirenz和非efavirenz的ART植入物的妇女的避孕失败或妊娠率。最后，对于目标3，我们将确定艾滋病毒阳性妇女、她们的伴侣和提供者如何就伴随的抗逆转录病毒疗法和避孕启动和选择作出决定，关于抗逆转录病毒疗法和避孕之间相互作用的潜在数据将如何影响她们的选择，并评估替代疗法和/或避孕战略的可接受性。我们假设，植入的依托诺孕酮浓度在接受基于efavirenz的抗逆转录病毒治疗后会降低，并且植入使用者的妊娠率将高于使用efavirenz的植入者。上述目标将是第一个全面解决基于efavirenz的ART和植入物之间相互作用的问题，在完成这个奖项后，Patel博士将处于一个极好的位置，提交一份R01，进一步推动 艾滋病毒和生殖健康方面的研究议程。

 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.