Views among Malawian women about joining HIV prevention clinical trials when pregnant.

BACKGROUND: The pressing need to expand the biomedical HIV prevention evidence base during pregnancy is now increasingly recognized. Women's views regarding participation in such trials and initiating PrEP while pregnant are critical to inform evolving policy and best practices aimed at responsibly expanding evidence-based access for this population. METHODS: We conducted 35 semi-structured interviews with reproductive-aged women in Malawi in the local language, Chichewa. Participants were HIV-negative and purposively sampled to capture a range of experience with research during pregnancy. Women's perspectives on enrolling in three hypothetical HIV prevention trial vignettes while pregnant were explored, testing: (1) oral PrEP (Truvada) (2) a vaginal ring (dapivirine), and (3) a randomized trial comparing the two. The vignettes were read aloud to participants and a simple visual was provided. Interviews were audio-recorded, transcribed, translated, and coded using NVivo 11. Thematic analysis informed the analytic approach. RESULTS: A majority of women accepted participation in all trials. Women's views on research participation varied largely based on their assessment of whether participation or nonparticipation would best protect their own health and that of their offspring. Women interested in participating described power dynamics with their partner as fueling their HIV exposure concerns and highlighted health benefits of participation-principally, HIV protection and access to testing/treatment and ancillary care, and perceived potential risks of the vignettes as low. Women who were uninterested in participating highlighted potential maternal and fetal health risks of the trial, challenges of justifying prevention use to their partner, and raised some modality-specific concerns. Women also described ways their social networks, sense of altruism and adherence requirements would influence participation decisions. CONCLUSIONS: The majority of participants conveyed strong interest in participating in biomedical HIV prevention research during pregnancy, largely motivated by a desire to protect themselves and their offspring. Our results are consistent with other studies that found high acceptance of HIV prevention products during pregnancy, and support the current direction of HIV research policies and practices that are increasingly aimed at protecting the health of pregnant women and their offspring through responsible research, rather than defaulting to their exclusion.

Ending the evidence gap for pregnancy, HIV and co-infections: ethics guidance from the PHASES project.

INTRODUCTION: While pregnant people have been an important focus for HIV research, critical evidence gaps remain regarding prevention, co-infection, and safety and efficacy of new antiretroviral therapies in pregnancy. Such gaps can result in harm: without safety data, drugs used may carry unacceptable risks to the foetus or pregnant person; without pregnancy-specific dosing data, pregnant people face risks of both toxicity and undertreatment; and delays in gathering evidence can limit access to beneficial next-generation drugs. Despite recognition of the need, numerous barriers and ethical complexities have limited progress. We describe the process, ethical foundations, recommendations and applications of guidance for advancing responsible inclusion of pregnant people in HIV/co-infections research. DISCUSSION: The 26-member international and interdisciplinary Pregnancy and HIV/AIDS: Seeking Equitable Study (PHASES) Working Group was convened to develop ethics-centred guidance for advancing timely, responsible HIV/co-infections research with pregnant people. Deliberations over 3 years drew on extensive qualitative research, stakeholder engagement, expert consultation and a series of workshops. The guidance, initially issued in July 2020, highlights conceptual shifts needed in framing research with pregnant people, and articulates three ethical foundations to ground recommendations: equitable protection from drug-related risks, timely access to biomedical advances and equitable respect for pregnant people's health interests. The guidance advances 12 specific recommendations, actionable within the current regulatory environment, addressing multiple stakeholders across drug development and post-approval research, and organized around four themes: building capacity, supporting inclusion, achieving priority research and ensuring respect. The recommendations describe strategies towards ethically redressing the evidence gap for pregnant people around HIV and co-infections. The guidance has informed key efforts of leading organizations working to advance needed research, and identifies further opportunities for impact by a range of stakeholder groups. CONCLUSIONS: There are clear pathways towards ethical inclusion of pregnant people in the biomedical research agenda, and strong agreement across the HIV research community about the need for - and the promise of - advancing them. Those who fund, conduct, oversee and advocate for research can use the PHASES guidance to facilitate more, better and earlier evidence to optimize the health and wellbeing of pregnant people and their children.

Malaria vaccine trials in pregnant women: An imperative without precedent.

Pregnant women are highly susceptible to Plasmodium falciparum malaria, leading to substantial maternal, perinatal, and infant mortality. While malaria vaccine development has made significant progress in recent years, no trials of malaria vaccines have ever been conducted in pregnant women. In December 2016, an expert meeting was convened at NIAID, NIH, in Rockville, Maryland to deliberate on the rationale and design of malaria vaccine trials in pregnant women. The discussions highlighted the progress made over recent years in the field of maternal immunization for other infectious diseases, and the evolving regulatory and ethical environment, all of which support a new emphasis on testing malaria vaccines that offer direct benefits to pregnant women. Initial safety and immunogenicity studies of malaria vaccines will be conducted in non-pregnant adult volunteers. Subsequently, efficacy trials involving pregnant women will likely be conducted in malaria-endemic and often resource-poor environments where sufficiently high malaria incidence will allow vaccine activity to be measured. Such trials will need to meet all international standards to ensure the safety of mother and offspring, under oversight of appropriate ethical and regulatory bodies. The convened experts drafted a clinical development plan to test a malaria vaccine product during pregnancy, using as a case study PfSPZ Vaccine being developed by Sanaria Inc. that is currently in phase 2 testing. Following the expert recommendations, a pregnancy registry has been initiated in Ouelessebougou, Mali, to provide baseline information on maternal and fetal outcomes as a context for evaluating PfSPZ Vaccine safety in the future, and new regimens are being assessed that will be suitable for evaluation in pregnant women.

Women's Views About a Paternal Consent Requirement for Biomedical Research in Pregnancy.

Clinical research to inform the evidence base to guide nonobstetrical care during pregnancy is critically important for the well-being of women and their future offspring. Conversations about regulations for such research, including whether paternal consent should ever be required, should be informed by the perspectives of those most affected, namely, pregnant women. We conducted in-depth interviews with 140 pregnant women living with or at risk of HIV-70 in Malawi, 70 in the United States-exploring their views on requiring paternal consent for pregnant women's participation in trials offering the prospect of direct benefit solely to the fetus. The majority of women supported such a requirement; others raised concerns. A trio of themes-the father's or pregnant woman's rights, fetal protection, and gender/relationship dynamics-characterized views both supporting and against a paternal consent requirement, expanding the range of considerations that should inform approaches to paternal involvement in research with pregnant women.