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岁少女和青年妇女的主要死因。尽管取得了进展， 在艾滋病毒治疗和预防方面，AGYW仍然处于高风险之中，特别是在撒哈拉以南非洲。经口预暴露 PrEP是一种非常有效的预防措施，有可能对艾滋病毒流行产生巨大影响。但迄今为止， 大多数在女性中进行的PrEP试验都无法证明有效性，主要是由于AGYW的依从性差。 新出现的证据表明，妇女可能更有可能使用一种艾滋病毒预防方法， 怀孕我们将测试一种干预措施，包括一个单一的口服胶囊提供PrEP和避孕- a 避孕多用途预防技术（cMPT）-与口服相比，作为增加PrEP依从性的策略 单独使用PrEP。我们将招募已经在津巴布韦哈拉雷使用COC的AGYW，那里的AGYW仍然很高 由于艾滋病毒的风险，超过一半的避孕妇女使用COCs，15-35岁的妇女中只有不到1%的人使用COCs。 制备型cMPT干预将包含两种市售产品：Truvada® [恩曲他滨和替诺福韦酯] 富马酸盐（TDF）]和复方口服避孕药（COC）[左炔诺孕酮（LNG）/炔雌醇（EE）]。本研究 将通过人口理事会之间的合作实施，人口理事会在临床试验方面具有全球专业知识， 实施科学，可行性研究和评价女性发起的艾滋病毒预防方法， 津巴布韦大学健康科学学院（UZCHS），在开展艾滋病毒临床研究方面有着悠久的历史。 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，以探讨 将Truvada与COC相结合，通过与AGYW的焦点小组讨论和深入研究， 与医疗保健提供者的访谈（IDIs）。在目标2中，我们将把形成性研究结果纳入 1）cMPT包装和客户信息材料的开发和预测试; 2）依从性和可接受性 问卷调查;以及3）提供者培训手册。在目标3中，我们将比较可接受性、偏好和依从性 cMPT干预与标准治疗（2种单独的药丸：Truvada®和COC）。在为期6个月的随机研究中， 在一项交叉研究中，津巴布韦哈拉雷的30名AGYW（16-24岁）将以随机顺序分配至以下序列： 2种治疗方案：cMPT干预或标准治疗（2片单独的药丸）。每种方案将使用3 28天 月经周期（每个疗程约3个月）。在6个月结束时，妇女将被要求说明他们的 偏好cMPT干预或2个单独的药丸。我们将评估和比较可接受性和依从性（通过 干血斑），以及社会生态因素（例如，个人、伙伴、家庭、诊所一级） 与依从性和可接受性相关。我们将与5名AGYW一起通过IDI探索促进因素和障碍 所有完成研究的人和所有提前退出的AGYW。现在获得确认， 与当前批准的产品一起实际使用的cMPT将加速此类产品在 市场。鉴于该项目的支持性发现，我们将概述一个监管批准更多成本的过程- 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.