PrEP and Risk Compensation: Assessing Effect and Preparing for Rollout

描述(申请人提供)：新的艾滋病毒预防方法，如口服暴露前预防(PrEP)，如果目前的临床试验证实其有效性和安全性，可能很快被批准用于艾滋病毒预防。未来使用者的风险补偿是一个主要问题，因为一旦推出，这可能会严重破坏PrEP对公众健康的潜在影响。目前，风险补偿仅在旨在评估PrEP有效性的临床试验中进行评估。但是，仅有关于风险补偿的临床试验数据不足以指导PrEP规划，因为这些数据是在最佳咨询情况下收集的，并且在社会合意答案的可能性增强的情况下收集。研究药物的未知有效性和安慰剂的存在也是对数据有效性的重大威胁。临床试验环境之外的研究需要为PrEP的推出做好充分的准备。在PrEP被批准用于艾滋病毒预防之前，现在进行拟议的研究，如果目前的试验证明PrEP的有效性和安全性，就可以对PrEP的推出做出快速反应。提出的研究包括三个目标，分两个阶段进行研究。每个阶段使用不同的方法，但通过一个基本的概念模型--信息、动机和行为(IMB)框架联系在一起。在第一阶段，在听到关于PrEP的信息后，来自撒哈拉以南非洲两个地点-肯尼亚的邦多和南非的比勒陀利亚-的600名妇女将随机接受两个因素类型调查中的一个。每项调查将使用相同的现实小插曲，但会因研究臂的PrEP背景而异--小插曲的参与者接受PrEP或不接受PrEP的插曲的参与者。调查数据将被用来解决研究的目标1和2：1)评估PrEP的可用性将对艾滋病毒感染风险较高的女性的性风险决策产生的影响，以及2)确定在使用PrEP时最有可能增加其性风险行为的女性的人口统计学和行为相关性。拟议研究的第二阶段将涉及目标3，即为使用PrEP时最有可能增加其性风险行为的女性制定降低风险咨询指南。将对每个网站进行深度访谈，每个网站有30名符合这一标准(根据调查数据确定)的妇女，每个网站最多有3名顾问。来自这些访谈的数据以及调查数据将被用于在IMB框架内创建降低风险咨询指南。指导方针将包括关键信息、激发关于风险感知的讨论的问题、识别最有可能表现出风险补偿的问题以及将风险补偿降至最低所需的行为技能。 公共卫生相关性：以抗逆转录病毒为基础的产品，如口服暴露前预防(PrEP)，在预防新的艾滋病毒感染方面可以对公共卫生产生重大影响，但风险补偿可能会大幅降低其益处。考虑到临床试验环境的人为因素，目前有关临床试验风险补偿的数据不足以预测临床试验环境之外的风险补偿。为了最大限度地提高PrEP在向公众推出后的好处，拟议的研究将评估PrEP的可用性对临床试验环境以外艾滋病毒感染风险较高的女性的性风险决定的影响。这项研究的结果将是为使用PrEP时最有可能增加性行为风险的女性提供降低风险咨询指南。

DESCRIPTION (provided by applicant): New HIV prevention methods such as oral pre-exposure prophylaxis (PrEP) may soon be approved for HIV prevention if current clinical trials confirm their effectiveness and safety. Risk compensation among future users is a major concern, as it could seriously undermine the potential public health impact of PrEP once rolled out. Currently risk compensation has only been assessed in clinical trials designed to evaluate the effectiveness of PrEP. But clinical trial data on risk compensation alone is not sufficient to guide PrEP planning given those data are collected in situations of optimal counseling, and where the potential for socially desirable answers is enhanced. The unknown effectiveness of the study drug and the presence of a placebo arm are also substantial threats to data validity. Research outside the clinical trial environment is needed to adequately prepare for PrEP rollout. Conducting the proposed research now, before PrEP is approved for HIV prevention, allows for a quick response to PrEP rollout if current trials demonstrate the effectiveness and safety of PrEP. The proposed research includes three aims and is investigated in two phases. Each phase uses a different methodology but is linked together by an underlying conceptual model - the Information, Motivation, and Behavioral (IMB) Framework. In Phase 1, after hearing messages about PrEP, 600 women from two sites in sub-Saharan Africa - Bondo, Kenya and Pretoria, South Africa - will be randomized to receive one of two factorial-type surveys. Each survey will use the same realistic vignettes, but will vary by PrEP context based on study arm - the participant in vignette taking PrEP or participant in vignette not taking PrEP. Survey data will be used to address Aims 1 and 2 of the research: 1) to assess the effect that the availability of PrEP will have on sexual risk decisions among women at higher risk for HIV infection, and 2) to identify demographic and behavioral correlates of women who are most likely to increase their sexual risk behavior when using PrEP. Phase 2 of the proposed research will address Aim 3, which is to develop risk-reduction counseling guidelines for women who are most likely to increase their sexual risk behavior when using PrEP. In-depth interviews (IDIs) will be conducted with 30 women per site who meet this criterion (as identified from survey data) as well as up to 3 counselors per site. Data from these interviews, as well as survey data, will be used to create risk-reduction counseling guidelines within an IMB framework. Guidelines will include key messages, questions to stimulate discussion on perception of risk, questions to identify those mostly likely to exhibit risk compensation, and behavior skills needed to minimize risk compensation. PUBLIC HEALTH RELEVANCE: Antiretroviral-based products such as oral pre-exposure prophylaxis (PrEP) can have a major public health impact in preventing new HIV infections, but risk compensation can drastically reduce its benefit. Current data on risk compensation from clinical trials are insufficient at predicting risk compensation outside of the clinical trial setting given the artificiality of the clinical trial environment. To maximize the benefit of PrEP once it is rolled out to the public, the proposed research will assess the effect that the availability of PrEP will have on sexual risk decisions among women at higher risk for HIV infection outside of the clinical trial environment. The study outcome will be risk-reduction counseling guidelines for women who are most likely to increase their sexual risk behavior when using PrEP.