The PHASES Project: Pregnancy and HIV/AIDS-Seeking Equitable Study

 描述(由申请人提供)：为全球1600万艾滋病毒携带者、美国28万艾滋病毒携带者以及数百万有艾滋病毒感染风险的妇女提供治疗和预防战略的证据，由于在伦理和法律上允许将孕妇纳入研究试验的不同阶段的问题和混乱而严重受挫。人们的担忧导致缺乏证据来指导艾滋病毒管理的紧迫领域，包括孕妇新的抗逆转录病毒药物的剂量、时间表和毒性、耐药结核病合并感染的治疗以及孕妇的预防性药物。这导致了不理想的护理，因为怀孕需要影响药物新陈代谢的生理变化，而且胎儿的存在引起了对安全性的特别关注。两者都强调了根据研究环境中收集的证据做出合理的治疗方案决定的重要性。相反，人们倾向于排除研究并将风险输出到临床环境中。在这个复杂和多方面的问题上取得进展，需要让研究、伦理、监管和法律界参与进来，为艾滋病毒研究和怀孕制定可持续和实用的前进道路。由NIH R56过渡性资金发起，由伦理、法律、艾滋病毒和妇女健康领域的国际公认领导者组成的团队领导，通过综合实证研究、利益相关者参与以及伦理和法律分析，阶段(怀孕和艾滋病毒/艾滋病：寻求公平研究)项目旨在制定指导方针，通过负责任的研究战略，促进感染艾滋病毒和面临艾滋病毒风险的孕妇的健康需求，特别是：1)通过与美国和南部非洲的艾滋病毒研究社区(包括艾滋病毒调查人员、IRB专业人员和政策官员)接触，扩大对开展孕期艾滋病毒研究的科学优先事项、感知的障碍和新颖的研究设计解决方案的确定；并通过与携带艾滋病毒或有艾滋病毒风险的孕妇的接触来表征参与此类研究的理由-在美国和非洲环境下，2)对孕妇进行负责任的艾滋病毒研究的条件进行学术法律和伦理分析，以响应这些优先事项、障碍和观点，并通过与学术和监管专家的反复接触而形成；以及3)制定并积极向艾滋病毒研究界传播一份具体的、参与驱动的指导文件，其效用已由一系列专家审查小组建立，规定何时以及在何种情况下应将孕妇纳入艾滋病毒研究。考虑到参与的不同群体、严格的设计以及调查人员的个人和协作经验，该项目将为怀孕期间的艾滋病毒研究确定一条明确的前进道路，这将有助于改变阻碍了高危或感染艾滋病毒妇女和子女健康的证据基础的政策和做法。

 DESCRIPTION (provided by applicant): Evidence to inform treatment and prevention strategies for the 16 million women living with HIV worldwide, 280,000 in the US, and millions more women at risk for HIV infection, is critically thwarted by questions and confusions about the ethical and legal permissibility of including pregnant women in various stages of research trials. Concerns have led to a dearth of evidence to guide pressing areas of HIV management, including dose, schedule and toxicity of new antiretrovirals for pregnant women, treatments for drug- resistant TB co-infection, and preventive agents for women who are pregnant. This leads to suboptimal care, since pregnancy entails physiologic changes affecting drug metabolism and the presence of the fetus raises particular concerns about safety. Both emphasize the importance of reasoned decisions about treatment regime, based on evidence garnered in research settings. Instead, the tendency has been to preclude research and export risk to clinical settings. Progress on this complex and multifaceted issue requires engaging research, ethics, regulatory and legal communities to develop sustainable and practical ways forward for HIV research and pregnancy. Initiated with NIH R56 bridge funding and led by a team of internationally recognized leaders in ethics, law, HIV and women's health and through integrated empirical research, stakeholder engagement, and ethical and legal analyses, the PHASES (Pregnancy and HIV/AIDs: Seeking Equitable Study) Project aims to develop guidance critical to advancing the health needs of pregnant women with and at risk for HIV through responsible research strategies, specifically: 1) To expand identification of scientific priorities in, perceived barriers to and novel research design solutions to the conduct of HIV research in pregnancy through engagement with the HIV research community in the US and Southern Africa, including HIV investigators, IRB professionals, and policy officials; and to characterize reasoning around participation in such studies through engagement with pregnant women with or at risk for HIV - in both U.S. and African settings, 2) To conduct scholarly legal and ethical analysis of conditions for responsible HIV research with pregnant women that is responsive to these priorities, barriers and viewpoints and developed through iterative engagement with academic and regulatory experts; and 3) To develop and aggressively disseminate to the HIV research community a Concrete, Engagement-Driven Guidance Document , whose utility has been established by a series of expert vetting panels, delineating when and under what circumstances pregnant women should be included in HIV research. Given the diverse groups engaged, rigorous design, and the individual and collaborative experience of the investigators, this project will identify a clear path forward for HIV research i pregnancy that will be instrumental in shifting policies and practices that have hampered the evidence base for optimizing the health of women and offspring at risk or infected with HIV.