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.
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 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.
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