Combining PrEP with contraception: a pilot test of an intervention to increase adherence to PrEP in adolescent girls and young women in Zimbabwe

艾滋病毒是15-24岁青春期女孩和年轻妇女死亡的主要原因。尽管取得了进展，但 在艾滋病毒治疗和预防方面，AGYW仍然处于高风险，特别是在撒哈拉以南非洲。口腔预曝光 预防措施(PrEP)非常有效，有可能对艾滋病毒流行产生重大影响。到目前为止， 大多数PrEP在妇女身上的试验都无法证明疗效，主要是因为AGYW的依从性较差。 新出现的证据表明，女性可能更有可能使用一种预防艾滋病毒的方法，这种方法也可以防止 怀孕了。我们将测试一种由提供PrEP和避孕的单一口服胶囊组成的干预-a 避孕多用途预防技术(CMPT)--与口服相比，作为提高PrEP依从性的策略 一个人做准备。我们将招收已经在津巴布韦哈拉雷使用COC的AGYW，在那里AGYW继续处于高水平 艾滋病毒的风险，超过一半的避孕妇女使用COCs，而在15-35岁的妇女中使用的不到1% 准备好了。CMPT干预将包含两种上市产品：Truvada®[恩曲他滨和替诺福韦异丙酚 富马酸(TDF)和一种联合口服避孕药(COC)[左旋诺孕酮(LNG)/乙炔雌二醇(EE)]。这项研究 将通过在临床试验方面拥有全球专业知识的人口理事会之间的合作来实施， 关于女性发起的艾滋病毒预防方法的实施科学、可行性研究和评估，以及 津巴布韦大学健康科学学院(UZCHS)，该学院在开展艾滋病毒临床研究方面有很长的历史 研究和预防研究。在目标1中，我们将进行定性的形成性研究，以探索 将Truvada与COC相结合，通过与AGYW的焦点小组讨论和深入讨论，提高PrEP的遵从性 与医疗保健提供者的面谈(IDI)。在目标2中，我们将把形成性研究成果纳入 开发和预先测试1)cmpt包装和客户信息材料；2)遵守和可接受 问卷调查；以及3)供应商培训手册。在目标3中，我们将比较可接受性、偏好和依从性 CMPT干预与标准护理(两种不同的药片：Truvada®和COC)的对比。在为期6个月的随机调查中， 交叉研究，津巴布韦哈拉雷的30名AGYW(16-24岁)将被随机分配到 两种方案：CMPT干预或标准护理(2个单独的药片)。每个疗程为3-28天。 月经周期(每个方案大约3个月)。在6个月结束时，女性将被要求陈述她们的 偏爱中药干预或2片单独用药。我们将评估和比较可接受性和遵从性(通过 2种方案的血斑)，以及社会生态因素(例如，个人、伴侣、家庭、诊所) 与坚持和可接受性有关。我们将与5个AGYW一起探索通过IDI使用的促进者和障碍 完成学习的人和所有提前退学的AGYW。现在正在确认对口头演讲的偏好 与当前批准的产品一起实际使用的cmpt将加快此类产品在 集市。鉴于此项目的支持结果，我们将概述监管部门批准更多成本的流程- 有效的联合配方药丸。

HIV is the leading cause of death in adolescent girls and young women (AGYW) aged 15-24 years. Despite advances in HIV treatment and prevention, AGYW remain at high risk, particularly in sub-Saharan Africa. Oral pre-exposure prophylaxis (PrEP) is highly effective and has the potential to make a dramatic impact on the HIV epidemic. Yet to date, most trials of PrEP in women have been unable to demonstrate efficacy, largely due to poor adherence among AGYW. Emerging evidence indicates that women may be more likely to use an HIV prevention method that also prevents pregnancy. We will test an intervention consisting of a single oral capsule providing both PrEP and contraception – a contraceptive multipurpose prevention technology (cMPT) – as a strategy for increasing PrEP adherence compared to oral PrEP alone. We will enroll AGYW who already use a COCs in Harare, Zimbabwe, where AGYW continue to be at high risk of HIV, more than half of contracepting women use COCs, and less than 1% of 15-35-year-old women are using PrEP. The cMPT intervention will contain two marketed products: Truvada® [emtricitabine and tenofovir disoproxil fumarate (TDF)] and a combined oral contraceptive (COC) [levonorgestrel (LNG)/ethinyl estradiol (EE)]. This research will implemented through a collaboration between the Population Council, which has global expertise in clinical trial, implementation science, feasibility studies and evaluation around female-initiated HIV prevention methods, and the University of Zimbabwe College of Health Sciences (UZCHS), which has a long history of conducting HIV clinical studies and prevention research. In Aim 1, we will conduct qualitative formative research to explore the acceptability of combining Truvada with a COC to increase PrEP adherence through focus group discussions with AGYW and in-depth interviews (IDIs) with healthcare providers. In Aim 2, we will incorporate formative research findings into the development and pre-testing of 1) cMPT packaging and client information materials; 2) adherence and acceptability questionnaires; and 3) a provider training manual. In Aim 3, we will compare the acceptability, preference, and adherence of the cMPT intervention versus standard of care (2 separate pills: Truvada® and COC). In a 6-month randomized, crossover study, 30 AGYW (16-24 years old) in Harare, Zimbabwe will be assigned in random order to the sequence of the 2 regimens: the cMPT intervention or standard of care (2 separate pills). Each regimen will be used for 3 28-day menstrual cycles (approximately 3 months per regimen). At the end of 6 months, women will be asked to state their preference for the cMPT intervention or the 2 separate pills. We will assess and compare acceptability and adherence (via dried blood spots) of the 2 regimens, and socioecological factors (e.g., individual-, partner-, family-, clinic-level) associated with adherence and acceptability. We will explore facilitators and barriers to use through IDIs with 5 AGYW who complete the study and all AGYW who withdraw early. Acquiring confirmation now on the preference for an oral cMPT from actual use with currently approved products will accelerate the availability of such a product in the marketplace. Given supportive findings in this project, we will outline a process for regulatory approval of the more cost- effective co-formulated pill.