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。我们将在津巴布韦哈拉雷招募已经使用联合口服避孕药(COCs)的AGYW，那里 AGYW继续处于感染艾滋病毒的高风险中，超过一半的避孕妇女使用COCs，15-35岁的妇女中不到1%- 一岁的妇女正在使用PrEP。Cmpt干预--一种双重预防药丸(DPP)--将包含两种上市的 产品：Truvada®[恩曲他滨和替诺福韦富马酸二异丙酯(TDF)]和COC[左旋诺孕酮(LNG)/乙炔 雌二醇(Ee)]。这项研究将通过人口理事会与全球人口理事会之间的合作来实施 关于女性发起的艾滋病毒的临床试验、实施科学、可行性研究和评估方面的专业知识 预防方法和津巴布韦大学临床试验研究中心(UZ-CTRC)，它有很长的历史 从事艾滋病毒临床研究和预防研究的历史。在目标1中，我们将进行质的形成 通过焦点小组探讨特鲁瓦达与COC相结合提高PrEP依从性的可接受性研究 与AGYW的讨论和与医疗保健提供者的深入访谈(IDI)。在目标2中，我们将纳入 对1)DPP包装和客户信息材料的开发和预测试的形成研究成果；2) 遵从性和可接受性问卷；以及3)供应商培训手册。在目标3中，我们将比较 DPP干预与护理标准的可接受性、偏好和依从性(两种不同的药片：Truvada®和 COC)。在一项为期6个月的随机交叉研究中，津巴布韦哈拉雷的30名AGYW(16-24岁)将被分配到 2个方案的顺序随机排列：DPP或标准护理(2个单独的药片)。每种疗法都将被使用 为期3个28天的月经周期(每个方案约3个月)。6个月后，妇女将被要求 说明他们对民进党或两种不同药丸的偏好。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。现在正在确认对民进党的偏好 从实际使用到目前批准的产品，将加快此类产品在市场上的供应。 鉴于此项目的支持结果，我们将概述监管部门批准更具成本效益的联合 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 combined oral contraceptives (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 – a dual prevention pill (DPP) – will contain two marketed products: Truvada® [emtricitabine and tenofovir disoproxil fumarate (TDF)] and a 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 Clinical Trials Research Centre (UZ-CTRC), 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) DPP 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 DPP 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 DPP 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 DPP 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 a DPP 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.