Our study surfaced the views of Malawian women at risk for HIV toward enrolling while pregnant in three hypothetical biomedical HIV prevention research studies using vignettes. The majority of women conveyed preliminary interest in participating while pregnant in the oral PrEP and vaginal ring studies and the RCT described by the vignettes. Five dominant themes with corresponding subthemes emerged from women’s descriptions of benefits and concerns about participating in the vignettes, some of which are specific to the modality: protecting the health of self and baby; power dynamics with partner; social influences; altruism, and adherence requirements.
The most prominent theme motivating women’s decisions surrounding vignette participation across participants was the desire to protect their health and that of their offspring, and the majority of participants believed that participating in the research vignettes was conducive to this aim. Women described a strong motivation to remain HIV-uninfected, both for their own health and that of their future offspring, mirroring previous findings [20,21,22]. Notably, no respondents said they were unconcerned about potential HIV infection during pregnancy. At the time of data collection, biomedical HIV preventives were not available in Malawi outside of a research context, so participation in the research vignettes would provide a benefit that is otherwise unavailable .
Concerns have been raised that access to biomedical HIV prevention products in a trial conducted in a context with high HIV prevalence and where PrEP is otherwise inaccessible may be so appealing to potential participants as to represent undue inducement ; this motivation may be even further heightened during pregnancy. However, classifying an inducement to participate as undue requires that it have a distorting impact on a participant’s ability to rationally weigh costs and benefits of participation . Given that women’s perceptions of HIV infection risk during pregnancy are well supported, their strong desires for protection rational, and their expectations that the trial intervention will reduce risk plausible, the inducement to participate here is reasonable, not undue . In particular, recent research has suggested the risk of HIV seroconversion may be elevated during pregnancy, likely due to both biologic and sociobehavioral factors [2,3,4,5,6,7]. Given that pregnancy may be a time of heightened risk of infection to the woman, and that seroconversion during pregnancy elevates the risk of vertical transmission , rather than questioning if women’s desire for protection may distort their decision making abilities, we may more appropriately consider the ethics of denying these women access to such trials .
HIV prevention was not the sole health benefit identified. Many participants, particularly those who were research experienced, described the desirability of the quality and breadth of care provided in a biomedical trial, which may be particularly salient during pregnancy. Prior research has found access to ancillary care to be a primary motivator in this setting for clinical trial participation , and ethicists have argued that such access in limited resource contexts is a legitimate consideration for participants and to some extent a duty for researchers to provide [37,38,39,40]. However, strong motivation to access ancillary care may also signal a potential blurring of the lines between research and clinical care in the eyes of prospective participants. It is thus important for participants to understand that the goals of research differ from the goals of care. For example, medical procedures may be performed not because they are standard of care or to benefit the participant, but as part of the study protocol. Our research, while not designed to address this topic, does raise important questions of how pregnancy might differentially affect motivation related to ancillary care access in research. Further research should explore and analyze ethical considerations related to decision making around trials which may be a point of access for antenatal care services otherwise unavailable.
Many women specified that their perceived risk of HIV infection was due wholly or partly to power dynamics with their partner, and described the trials as a way to protect themselves against HIV exposure during pregnancy due to partner infidelity. However, relationship power dynamics also discouraged participation for numerous research inexperienced respondents who expressed concerns that participation may result in tensions with their partner surrounding accusations of undisclosed HIV status—either the woman herself being accused or her partner feeling accused of being HIV-infected. In work previously published with this sample on the topic of paternal consent for research participation, some participants cited fear of relationship conflict, including fears of violence, as influencing their views . Those with prior research experience during pregnancy did not mention this fear as a deterrent to participation, which may be either because their prior participation in HIV prevention research reduced this barrier, or it wasn’t an issue for them to begin with. Alternatively, given our recruiting methods , none of the research experienced women were currently pregnant, whereas all of the research inexperienced women were. Though we asked all women to imagine they were pregnant when responding to the vignettes, certain concerns, including potential relationship conflict over research participation during pregnancy, may have been more readily imaginable to those who were currently pregnant. These findings expand understanding of the wide range of ways in which relationship power dynamics can affect women’s orientations toward research participation during pregnancy in African settings , and suggest a potential influence of prior HIV prevention research experience during pregnancy on their perceptions of power dynamics with their partner surrounding study enrollment. Understanding this factor as both a potential motivator and potential deterrent may be helpful in future community engagement efforts around HIV and other sexually transmitted disease related research with pregnant women, particularly when engaging male partners.
Community engagement efforts for future research with pregnant women may also be informed by the modality specific concerns raised by participants in our study. While concerns raised are consistent with prior work with women considering HIV prevention options [20,21,22], fears of HIV stigma surrounding PrEP initiation may be heightened in the context of pregnancy and should be further explored. For example, some women expressed fears that participating in an oral PrEP trial will lead to assumptions by family and/or community members that she is HIV positive and engaged in risky sexual behaviors. Fear of this potential stigma may be heightened during pregnancy and carry greater social repercussions, when reliance on one’s social network can increase. Additionally, concerns about the physical effects of HIV prevention modalities may raise distinct concerns due to the presence of the fetus (e.g., reported concern for fetal entanglement with the vaginal ring).
Our findings are consistent with limited prior research examining research experienced and inexperienced healthy volunteers’ perspectives on clinical research protocols, in that the majority of considerations identified overlapped . In addition to differences regarding the effect of power dynamics with their partner, other distinctions included the encouragement of friends as a supporting factor and the challenges of daily oral PrEP adherence as a dissuading factor only for research experienced women. These concrete and specific concerns appeared to result from past research experiences which provided context in considering hypothetical vignettes. While no women interviewed had prior experience in an oral PrEP trial, some had experience with other prevention modalities, which may have illuminated potential challenges of adherence. In contrast, research inexperienced women lacked such experience, making their decision making more theoretical.
Several respondents noted concerns that would affect adherence. Certainly, adherence to PrEP is a broad concern generally, and not only in pregnancy [42,43,44]. In response to the well documented barriers to PrEP adherence, significant research efforts have focused on how best to motivate and support uptake and adherence, and have informed development of the next-generation of preventives designed to lower such barriers. Accounting for modality-specific concerns, including those that might specifically affect adherence in pregnancy, will be important to the generation of clinically useful data and effective implementation of new preventives in pregnant women.
It is worth noting that many women were also positively oriented towards the RCT vignette. While concerns in the ethics literature around randomization during pregnancy have primarily centered around the ethics of randomizing pregnant women to placebo arms [45,46,47], others have suggested that women who are pregnant may be generally disinclined to randomization given aversion to uncertainty [48, 49] and the importance to women of control during pregnancy . However, concerns around being randomized to one of two active trial arms were uncommon barriers to participation in this study. Only two of the women who responded positively to both the oral PrEP and ring trials were uninterested in the RCT. In contrast, three women who had refused either the oral PrEP or the ring trials responded positively to the RCT, noting that they would simply drop out of the study if they weren’t randomized to their preferred product. These findings suggest that assessing intent to remain in a RCT regardless of study arm assignment during the informed consent process may help to reduce attrition rates.
Despite prior concerns in the literature around pregnant women’s willingness to join biomedical research generally [51, 52], we found many women would be willing, and in some cases, highly motivated, to participate in HIV prevention trials in this context. These findings provide support for several vanguard HIV prevention studies with pregnant women currently underway or in development, including IMPAACT 2009, which examines oral PrEP use during pregnancy and postpartum, and MTN-042 (DELIVER), which plans to randomize pregnant women to oral PrEP or the vaginal ring during pregnancy in the Malawian and comparable settings [53, 54]. Work to surface women’s perspectives on PrEP use in the context of pregnancy is ongoing to support MTN-042 .
The purpose of our methodology was to surface women’s initial receptiveness, and perceived potential benefits of and concerns about participation in HIV prevention trials while pregnant. The brief vignettes provided an overview of the studies, and did not include the detailed information contained in a standard informed consent process including potential risks to participants; without this information, respondents did not commonly foresee potential risks. Thus the actual enrollment decision participants would make in real life scenarios cannot be predicted from our findings.
The methodology was designed to identify factors influencing women’s views on HIV prevention research participation during pregnancy in the Malawian context. The relatively small sample is not representative of all women at risk of HIV in Malawi, nor women of reproductive age more broadly, and the findings cannot be generalized to these populations. Just over half of our sample was research experienced during pregnancy. While the overall sample may not be representative of the range of women who might be candidates for research, our sampling approach allowed us to capture a range of prior experiences of research that might inform decisions about participation, from being denied enrollment in a study due to pregnancy, to being removed from a study product when pregnancy occurred many months into trial participation. We were also able to capture the views of some women who had not previously been involved in research. Together the groups are representative of a range of women who may be recruited for study participation in the future and therefore offer important perspectives to consider.
Finally, our study did not explore women’s views on participating in biomedical research while pregnant for the full range of HIV prevention products in the development pipeline, including long-acting injectable cabotegravir , and ultra-long-acting, removable dolutegravir . These products offer potentially important advantages, including simplified adherence, and added discreetness. As these products are developed, future studies should continue to explore women’s opinions on using these modalities during pregnancy in both research and clinical contexts.