The study explored the expectations and experiences of HIV vaccine trial participants. Six themes emerged around positive and negative trial expectations, negative community interpretation of the trial, trial public health benefits to participants, safety issue and the impact of clinical procedures on participants’ routine lives. We interpret the findings in terms of the ongoing HIV vaccine development and draw lessons for COVID-19 vaccine trial development. The findings help in understanding participants as vital contributors to vaccine development. We believe that the success of any vaccine trials hinges on the feedback of participation from participants without which results would be difficult to interpret.
We found that the success of a trial depends on direct and indirect participation in trials. That not only participants but also the significant others played a part in the trial participation requires more thought in view of the COVID-19 that the world is faced with. This demonstrates that the success of any vaccine trial is not solely on the drug but on a holistic consideration of participants including those who do not complete the trial, community members as well as the collaborators.
We learnt in our vaccine trial and other similar trials before (25–27) that it is important to understand that COVID-19 vaccine trial development has multiple players who are either direct and indirect and help to make the trial a success or a failure if not handled appropriately. Direct players include participants themselves while indirect players include spouses, family, community, dropped participants, organizers - local and international collaborators. COVID-19 vaccine trial investigators can learn from real and expected collaborative engagements from our study which participants and communities imagined and ideally imposed onto the trial.
We found participant and community misconceptions and myths about the vaccine trial such as that participants were infected with a live virus and others on false positivity. These were magnified by the participant’s concerns on the safety of the vaccine on trial. Participants’ and community’s beliefs, concern and fear of being inoculated with a live HIV virus and the concern that the trial was sacrificing Africans as guinea pigs is not a new fear. Other studies reported the same concerns before (26, 27).
The fear that participants will be injected with a live vaccine should be debated in the context of human challenge studies which scientists including at the WHO consider as not outside the tools that should be deployed in the search for a vaccine for COVID-19 (28). Should such studies be implemented, detailed information sessions should be considered to enable ethically acceptable methods of conducting the studies. In this case, the launch of vaccine trials for COVID-19 has not been without the same challenges including hesitancy and fear of the unknown if one gets vaccinated(6). Demystifying myths through a program of education is required to ensure participants and their communities are properly educated on trials (11) A lesson for current and future studies is that trust in the governments and research authorities are needed to dispel community and participant fears. Building communities of trust is crucial for the success of vaccine trials. As the world gears up for a vaccine for COVID-19 lessons learnt in the search for an HIV vaccine trial are hugely important today.
Those participants referred to investigators as foreigners to them suggest that trials’ investigators must have a shared identity with participants. Previous studies in South Africa also reported on challenges of mistrust as a result of a racial identity that was not shared between participants and investigators (25) resulting in the black participants thinking that they may have been at risk of vaccine-induced infection into the participant of the other racial identity by another of the racial and foreign identity. This again is similarly shared in vaccine trials in South Africa (25). Continuous education of the community would go a long way clearing the misconceptions and avoiding such misconceptions from wrongly influencing participants. For example, vaccine trials for COVID-19 which some two French doctors suggested must be tested in Africa (www.bbc.com/news/world-africa-52192184) were actually conducted first in China and the developed world before any was launched in Africa (29). This was followed by an educational announcement by the WHO Director-General in setting the record straight that vaccine development would not be any racial but would follow established ethical protocols.
The researchers are urged to build communities of practice and meaningful collaborations with local settings and communities for proper information dissemination and for meaningful involvement of local people in trials. Examples of meaningful involvement include setting up community management and information dissemination teams in the communities where participants are recruited. This helps to bring communities to plan and contribute to the trial. Robust engagement with the study community and participants is required for COVID-19 vaccine trials. However, Shah et al encourages context-specific public engagement to minimize contact while maintaining social distancing regulations which can be through virtual platforms in well-resourced settings (30) or must be made available in resource limited settings. In addition, selecting sites must avoid mere convenience or vulnerability but to maximize trust between participants and investigators.
We also learnt that participants join the study for exterior motives such as to benefit humanity or in the words of the participants, to be part of the world’s efforts to fight the HIV epidemic and protect future generations. A similar study in Kenya found that one-fifth of their participants were motivated by the need to find a vaccine for future generations (31). It is commendable that participants join trials for the benefit of others and not themselves. The ravaging effects of the HIV infection in the research community ignited participation out of altruistic. Likewise, the shocking death toll, excruciating pain with which COVID-19 brought may easily help to motivate participants to participate in the trial where they do not know if the vaccine will be safe to them of not. Such altruistic behavior is commendable and must be supported.
The COVID-19 will successfully rely on the commitment of participants to this important goal of benefitting humanity and not necessarily themselves. The public health benefits that were brought with the trial, such as free HIV testing and health insurance were not much cited by participants as motivations but benefits which came the way of participants. We cited the case of a healthy participant who accidentally fell ill and all his hospitalization and excellent care and bills were taken care of by the trial resources. Other studies in Tanzania have similarly reported participants being so grateful for medical insurance as a key benefit ( Tarimo et al., 2019). This may be because of lack of health insurance among people in resource-limited countries and communities.
In the United States people of lower socioeconomic groups including those from Hispanic origin were more likely to volunteer to obtain better access to resources that they did not have (33). As a result, study investigators must ensure that such participants from low-income groups who volunteer are properly protected and understand the study aim, procedures and possible harm. Participants for COVID-19 vaccine trials may also have similar considerations of threats and benefits that they need to weigh in the trial. Providing best available health insurance to participants during the COVID-19 trials should be a priority during the COVID-19 pandemic even at a time when the health system is overwhelmed by challenges including laboratory, human resources, hospital bed shortages that are commonly reported in many countries affected by COVID-19.
The organization of the vaccine trials around community settings and the selection and monitoring of volunteers require careful analysis of participants and the needs of the trial. In our study, the timing of visits to the clinic (morning hours and weekdays) brought some inconvenience to participants like students, employees and other participants with competing for daily schedules. A similar challenge has been reported in the previous phase I/II trials in which as many as 29 clinic visits interfered with normal lives of participants (34). We recommend addressing such challenges beforehand in the best possible ways to avoid them influencing the safety and effectiveness of the candidate vaccine. Where possible, introducing some form of flexibility to participants such as weekend attendance for participants who cannot attend due to competing economic activities is crucial.
In this study, it becomes evident that more and detailed information or clarifications about the trial procedures and outcomes are needed during the educational and information seminars to deal with volunteers’ worries and concerns on vaccine safety. This underlines the importance of improving the package of information to the volunteers, for example, information on the nature of the candidate vaccine to assure the volunteers that they will not get infection due to participation in the trial and also the vaccine-induced positivity due to antibodies from the vaccine. Information is power, if participants are empowered with the correct information, they withstand unnecessary misinformation, myths and misconceptions from community members and also help educate them including to accept trial procedures in future studies.
The study has its limitations. Firstly, the study was conducted three years post participation in the trial and the participant’s stories may have been subject to recall bias. Participants may have only concentrated on what they remembered most, leaving other stories which may have been important to the researchers. However, participant responses during the survey did not show any signs of recall challenges. Secondly, the opinions and experiences gathered with regards to the rumors and misconception about the trial in the community were only collected from the people who participated in the study. The study should have also interviewed community members to triangulate information with that obtained from participants for a more understanding of issues related to participation in vaccine trials. Despite these, we believe that we obtained a balanced view of the expectations and experiences of participation in the study. We also believe that these expectations and experiences are crucial for COVID-19 vaccine trial development.