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.

Public Health Relevance

The proposed research is relevant to public health because redressing the ethical and regulatory barriers to HIV research with women who are or may become pregnant is crucial to providing safe and effective treatment for prevention and treatment of HIV and its comorbidities in women and their offspring. The proposed research is relevant to NIH's mission to reduce the burdens of illness and disability, through development of clear ethical and regulatory guidance for the conduct of morally complicated HIV research that is crucial to effective prevention and treatment of HIV in women. Rigorously developed guidance for the conduct of ethically complex research advances the NIH's goal to promote scientific integrity and social responsibility in the conduct of science.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
High Priority, Short Term Project Award (R56)
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Special Emphasis Panel (ZRG1-AARR-F (57))
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Dawson, Liza
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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Mastroianni, Anna C; Henry, Leslie Meltzer; Robinson, David et al. (2017) Research with Pregnant Women: New Insights on Legal Decision-Making. Hastings Cent Rep 47:38-45
Krubiner, Carleigh B; Faden, Ruth R; Cadigan, R Jean et al. (2016) Advancing HIV research with pregnant women: navigating challenges and opportunities. AIDS 30:2261-5
Cohen, Jessica A; Mastroianni, Anna C; Macklin, Ruth (2014) Ethical issues for late-stage trials of multipurpose prevention technologies for HIV and pregnancy. Int J Gynaecol Obstet 127:221-4