Advancing HIV Research in Pregnancy; ethics and engagement

描述（由申请人提供）：为全球1590万感染HIV的女性（美国有39万）以及数百万有HIV感染风险的女性提供治疗和预防策略的证据受到伦理和监管问题的严重阻碍，这些问题涉及正在或可能怀孕的女性。人们的担忧导致缺乏证据来指导艾滋病毒管理和预防的紧迫领域，包括新抗病毒药物对妇女和后代的剂量，时间表和毒性，耐药结核病的治疗，以及正在或可能怀孕的妇女的预防药物，导致次优护理。我们假设，缺乏一个特定的伦理框架怀孕和怀孕的风险，以及缺乏足够的监管指导，严重阻碍了研究，以满足这一人群的需求。要在这一复杂和多方面的问题上取得进展，就需要让研究、伦理、监管和法律的界参与进来，就艾滋病毒研究和怀孕的可持续和切实可行的前进道路达成共识。本研究由国际公认的伦理、法律、艾滋病毒和妇女健康领域的领导人团队领导，通过综合的经验和伦理分析，旨在制定关键指导，通过负责任地参与研究，促进感染艾滋病毒和有感染艾滋病毒风险的妇女及其后代的健康需求，具体而言：1）通过与艾滋病毒调查人员的接触，确定开展艾滋病毒研究和妊娠的科学优先事项、感知障碍和潜在的新颖研究设计解决方案，临床研究伦理学专家、人类受试者监管和药物开发方面的法律的专家以及IRB专业人员;（二）为妊娠期艾滋病毒研究制定一个概念性伦理框架，以应对这些优先事项和当前的障碍，并至少包括对最低风险的含义和解释的谨慎处理，妊娠背景下的风险超过最小风险和妊娠可能性;不同但相关方之间的风险和获益裁定（妇女、胎儿、婴儿、性伴侣）;以及，将离散的医疗和医疗外风险纳入的怀孕风险和伤害概念;（3）在该框架的基础上，制定并积极传播一套关于艾滋病毒和妊娠研究的实用共识指导建议，这些建议在当前的监管环境下是可行的，其实用性和可接受性已经过HIV调查人员、感染HIV或有感染HIV风险的孕妇、研究伦理、法律法规和IRB专家的审查。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，该项目有可能改变政策 （b）在艾滋病毒/艾滋病领域，应采取措施，消除艾滋病毒/艾滋病的危害和做法，并纠正那些妨碍以证据为基础优化有感染风险或已感染艾滋病毒的妇女和后代健康的道德问题。

DESCRIPTION (provided by applicant): Evidence to inform treatment and prevention strategies for the 15.9 million women infected with HIV worldwide, 390,000 in the US, and millions more women at risk for HIV infection are critically thwarted by ethical and regulatory concerns about research with women who are or might become pregnant. Concerns have led to a dearth of evidence to guide pressing areas of HIV management and prevention including dose, schedule and toxicity for women and offspring for new antivirals, treatments for drug- resistant TB, and preventive agents for women who are or might become pregnant, leading to suboptimal care. We hypothesize that the absence of an ethical framework specific to pregnancy and the risk of pregnancy, and the absence of adequate regulatory guidance, have seriously hampered research to address the needs of this population. Progress on this complex and multifaceted issue requires engaging research, ethics, regulatory and legal communities to develop consensus around a sustainable and practical way forward in HIV research and pregnancy. Led by a team of internationally recognized leaders in ethics, law, HIV and women's health and through integrated empirical and ethical analyses, this study aims to develop guidance critical to advancing the health needs of women with and at risk for HIV and their offspring through responsible inclusion in research, specifically: 1) To identify scientific prioriies in, perceived barriers to, and potential novel research design solutions to the conduct of HIV research and pregnancy through engagement with HIV investigators, experts in clinical research ethics, legal experts in human subjects regulation and pharmaceutical development, and IRB professionals; 2) To develop a conceptual ethical framework for HIV research in pregnancy that is responsive to these priorities and current barriers and that will include at minimum careful treatment of at least the meaning and interpretation of minimal risk and more than minimal risk in the context of pregnancy and potential for pregnancy; adjudication of risks and benefits among different but related parties (woman, fetus, baby, sexual partners); and, concepts of risk and harm in pregnancy that incorporate discrete medical and extra- medical risk; and 3) Based on the framework, to develop and aggressively disseminate a set of practical consensus guidance recommendations on research with HIV and pregnancy that are actionable within the current regulatory environment, whose utility and acceptability have been vetted by HIV investigators, pregnant women with or at risk of HIV, and experts in research ethics, law and regulation, and IRBs. Given the diverse groups engaged, rigorous design, and the individual and collaborative experience of the investigators, this project has the potential to shift policies and practices and redress the ethical problems that have hampered the evidence base for optimizing the health of women and offspring at risk or infected with HIV.