Participating in HIV Prevention Clinical Trial: Reasons and Experiences among Female Participants in Antibody Mediated Prevention Study at UNC Project, Malawi

Aim : The overall aim of the study was to assess the reasons and experiences of participants involved in Antibody Mediated Prevention (AMP) HIV prevention clinical trial at University of North Carolina (UNC) Project, Lilongwe, Malawi. We determined the participants’ reasons for participating in HIV Prevention clinical trials; and the experiences of participants in HIV Prevention clinical trials. Methods : We adopted the qualitative cross-sectional study method. Data were collected using in-depth interviews (IDIs). Purposive sampling was used to select 12 study participants who consented to take part in the study. All participants were the ones taking part in the AMP HIV prevention study at the UNC Project. Data analysis was done concurrently with data collection using content analysis. Results : Individuals were motivated to participate in HIV research due to a range of perceived benefits. These included personal, health, and financial benefits. Participants' research experiences and their continued participation in HIV research were influenced by the research clinic context and the nature of their interactions with research staff. Conclusion ; When the clinical trial study participants’ expectations are met through what they experience in the study, the chances of them adhering to the study visits and procedures are high. Even for those who did not have any expectations prior to the study, feeling welcomed and being able to open up to the study staff encouraged their continued participation. In the end, this outweighed the negative comments made by the people in their communities or their friends


Introduction
Since the beginning of the HIV epidemic, over 75 million people have been infected with HIV and about 32 million people have died due to the virus [1]. At the end of 2018, more than 37.9 million people were living with HIV [1]. Increasing rates of HIV infection have characterized the Acquired Immune-Deficiency Syndrome (AIDS) epidemic in Sub-Saharan Africa with an estimated 25.5% of 78 million HIV infected people living in sub-Saharan Africa [2] .Malawi is one of the African countries that have been affected by the epidemic of HIV and AIDS, with 900,000 people aged  currently living with HIV in the country [3]. experiences with respect to autonomy, safety, and satisfaction can help researchers: enhance human subjects protection, including informed consent; enhance recruitment and retention; improve the quality of clinical research processes; and increase public trust in the research enterprise [7]. HIV Prevention Trials Network (HPTN) studies evaluate new HIV prevention interventions and strategies in populations and geographical regions that are bearing a disproportionate burden of infection. This is intended to facilitate rapid scale-up of proven interventions and to have the greatest possible impact on the pandemic [8].
One of the clinical trials is the Antibody Mediated Prevention (AMP) study [9]. The Understanding the socio-economic and cultural context in which these products are being evaluated, and are likely to be introduced is crucial to identifying the factors that may facilitate or hinder their use in future.
The perceptions and experiences of women taking part in HIV prevention trials were explored in Soweto, South Africa whereby the central finding was that the participants felt the sense of empowerment in spite of their being embedded in a culture that has come to fear, deny, or ignore AIDS [12]. Currently, there is no information on reasons and experiences of research participants in the AMP study at UNC project, Malawi.
Therefore, this study aimed at filling this gap in the Malawian context. 5 The aim of the study was to source information on the reasons, experiences, and challenges of female participants in AMP study, Lilongwe research site. This information will hence be useful for the design and implementation of future HIV prevention clinical trials, as well as the provision HIV prevention and care for women and the Malawian population at large.

Type of research study
This was a qualitative cross-sectional study which used in-depth interviews (IDIs) to collect data. A cross-sectional study design is a type of observational study design in which the investigator measures the outcome and the exposures in the study participants at the same time. The participants in a cross-sectional study are selected based on the inclusion and exclusion criteria set for the study. Once the participants have been selected for the study, the investigator follows the study to assess the exposure and the outcomes. In this study, the exposure was their participation in the study, while the outcomes were there experiences in the main AMP study [13]. Qualitative research is critical in unpacking social contexts and understanding phenomena in their natural setting [14]. The research design enabled the investigator to gain an in-depth understanding of participants' reasons and experiences in participating in HIV prevention clinical trials, mainly the AMP study.

Study place and population
The study was conducted at UNC Project within the Kamuzu Central Hospital (KCH) campus, Lilongwe -Malawi. The study was conducted among female participants involved in the AMP study; one of the HIV prevention clinical trials being conducted on site.
[10]. 6 The study recruited women among the 100 participants who were enrolled and actively participating in the Antibody Mediated Prevention (AMP) study, an HIV prevention trial currently being conducted at the UNC Project, Lilongwe. The enrolled participants in the main AMP study are given cash stipend as transport reimbursement. Purposive sampling method was used to select approximately 20 participants aged 18 to 35years from the 100 participants enrolled in the main AMP study. Purposive sampling is a nonrandom sampling which employs a deliberate choice of an informant based on the qualities the informant poses [15]. This is the technique whereby informants with desired characteristics and knowledge regarding the problem and research question are selected. Therefore, the selection of participants is based on the likelihood of the informant to provide adequate information required to respond to the research question.
Only 12 participants were interviewed out of the planned 20 participants because saturation was reached on the way as the responses became similar.

Inclusion and Exclusion criteria
Participants were eligible to participate upon meeting the set inclusion criteria. Eligible participants were female participants enrolled in AMP study; 18 to 35 years of age; and willing to participate in the study. The study excluded participants who were not willing to participate in the study, and all participants not available during the study period.

Study period
The research study was conducted for a period of 5 months (from September, 2018 to February, 2019). The activities started from the beginning of research assistant training and data collection using In-depth Interviews (IDIs), transcription of data, data analysis, and report writing. A total of 12 female participants enrolled in AMP HIV Prevention clinical trial were purposively selected from a list of all participants in the study. The participants were selected based on the fact that they share the same characteristics. This was done so to ensure that each participant involved in the AMP HIV prevention clinical trial was

Sampling strategy
given an equal chance of participation. The accepted technique used in qualitative research to determine sample size is that of saturation [16]. Data saturation refers to the point in the research process when no new information is discovered in data analysis, and this redundancy signals to researchers that data collection may cease. It is a point at which observing more data will not lead to discovery of more information related to the research questions [17,18]. During the study, data saturation was reached after interviewing 12 participants. Data saturation is reached when there is enough information to replicate the study when the ability to obtain additional new information has been attained, and when further coding is no longer feasible [16]. Qualitative inquiry assumes that information is collected until redundancy and saturation are reached [16,19].

Data collection
Data addressing the study objectives was collected using in-depth interviews which were conducted in Chichewa language. IDIs are a form of discussion or directed conversation between a researcher and a respondent designed to reveal the underlying motives of the interviewee's attitudes, behaviour, and perceptions [20]. The IDIs were used to deeply explore the point of view, feeling, and perspectives of participants. The IDI allowed the participants to express their story in their own voice. This helped in exploring the participants' experiences of participating in the HIV prevention clinical trials. The study used 12 in-depth interviews with its respondents to collect data. The PI and research assistant who was not directly involved in the AMP study, and was 8 selected based on research experience and orientation on the questionnaires, conducted data collection and transcription from 29 th October -18 th December. The interviews were conducted during AMP study clinic visits at the UNC Project, Lilongwe. All interviews were audio recorded to ensure that vital information is not lost during transcription.

Data management and analysis
The study PI conducted spot checks during data collection to ensure compliance to the study protocol. At the end of each day a meeting was set up with the research assistant to address any challenges faced during data collection. During this process, the PI and the research assistant debriefed on how the interviews were being conducted. Any issues were addressed before the next data collection process. The interview recordings were translated from Chichewa to English by the PI and to ensure consistency of data, the translations were checked by an independent person. Transcription of the data was carried out by the PI and the research assistant concurrently with data collection. Audio recordings were translated verbatim. Each transcription was labelled with the interview identification code which was assigned to the participant during the interview.
Transcribed data was checked by the PI against the recorded data to ensure that there was no misinterpretation of data.
Data was analysed using inductive content analysis, which is also known as the bottom up approach of content analysis. In inductive reasoning, specific observations and measures are evaluated, then patterns and regularities are detected, which is followed by formulation of some tentative hypotheses that can be explored, and finally general conclusions or theories developed [21]. A thematic analysis approach was followed during the data analysis process to extract key themes and the supporting themes.
Thematic analysis is the process of identifying patterns or themes within qualitative data. This involves a rigorous process of data familiarization, data coding, theme development, and theme revision [22]. Subsequently, codes were generated as they emerged from the data, and grouped thematically within and across study areas.
Analysis entailed development of a codebook, coding of the data, developing a list of emerging themes, categorizing the themes within a hierarchical framework of main and sub-themes, looking for patterns and associations between the themes, and comparing and contrasting within and between the different groups of participants. Findings from the analysis were summarized, compiled and used to develop recommendations and final report.

Study limitations
The conduct of the study was dependent on participants' AMP study visit schedules, therefore we had to wait for the participants to report, but the interviews were successfully done.

Ethical considerations
The involvement of contact with human subjects in research studies requires that the internationally accepted ethical standards in conducting all study activities are followed.
Ethical clearance for conducting the study was sort from the College of Medicine Research and Ethics Committee (COMREC). Further permission was obtained from the Country Director of UNC Project for the study to be conducted in the respective HIV prevention clinical trial. To ensure study participants' privacy, all study staff were carefully trained in human subjects' protection, especially the importance of protecting privacy and confidentiality and obtaining informed consent from each study participant using the approved consent forms. Research participants were informed of all risks and protections in the written consent form. Participants were also informed of their right to withdraw from the study and not to answer any questions they did not feel comfortable answering. Confidentiality of the individual responses was observed to the greatest extent possible. This was done by the use of random numbers instead of the participants names. All data and other information was maintained confidentially and kept anonymous.

Characteristics of participants
Twelve AMP study participants consented and participated in this study, all of which were HIV non-infected females. The participants' demographic characteristics collected were age which ranged from 18 to 35 years, education, and employment status.

Source of study information
The study participants were informed of the AMP study either through their friends in their communities who had the information on the study or were already participating in one of the studies at the UNC Project; or through the community educators from the project.

Motivators to study enrolment
Participants in the study had various reasons that motivated them to enrol into the study, majority of which said they anticipated to benefit more towards their health as they made their decision to join the study. Other motivators included financial benefits and just willingness to help the society. Despite hearing of the trial from different peoplesome heard it from friends, relatives and others heard it from the community teamthat did not have an impact on their decision to whether to enrol or not, crossing out influence from others as a reason for enrolment. When interviewed, participants in the AMP study gave a range of reasons as to why they took part in the study as well as what they were expecting as presented in the findings.

Health benefits
The participant's health was a key factor in their decision to enrol in the study or not.
Either because they felt at risk of contracting HIV or prior to being enrolled, they had been diagnosed with another disease. Of the participants interviewed, most of them perceived to be at risk of contracting HIV and so they needed to protect themselves.
Knowing themselves to have more than one sexual partner, they felt at risk of contracting HIV and so taking part in the AMP trial provides them the ability to protect themselves regardless of not knowing whether they are being given active drips or placebo.
Not knowing the kind of drip they are being given came up as a concern for some participants who felt that if they knew, they would protect themselves better. However, as part of the study, they are encouraged to use condoms which they were given. This gave them the surety that if not the medicine in the drip, at least their condom use will help them prevent HIV although still, some reported inconsistent use of condoms because they believed they were being protected by the medication in the drip.
Regardless, they felt it was better to be in the study and monitor their health unlike not enrolling. This is in line with Andisen and Newman's concept of need factors whereby the way people perceive their own general health and experience symptom of illness, pain, and worries about their health will influence their health seeking behaviour.
For some, the discomforts and uncertainty that came with participating in the study, like pain when the drip is being inserted were outweighed by the benefit of being able to protect themselves long term. They were sure that even if something were to happen, for instance side effects because of the medicine, they would be assisted by the clinic stuff and did not see a need to stop taking part in the study.
Access to better health services that are offered to the study participants was among the reasons as to why most participants felt the need to participate in the AMP study. This is consistent with the findings of the study in Brazil on motives for participating in clinical trials [24]. During the AMP study, participants who are diagnosed with other health problems are given care directly at the study site by health workers. A good number mentioned being tested for other diseases including STIs which they mostly did not know they had. Before the study, most participants reported not knowing that they had a certain disease but only knew about it after they enrolled in the AMP study.
The more they remained in the study, the more opportunities they had of knowing if there is anything in their bodies that needs medical attention and once diagnosed with any disease, they reported getting treated from them which when they compared to the way treatment is offered in normal healthcare settings, would not be the case.
The participants reported that at a normal clinic or hospital, they have to wait in line for a while before they are treated. After waiting, they are told that the hospital does not have the medicine needed to treat their illness. This was the case when they (the participants) fall sick even if it is not a study related sickness when their children fall sick as they were being treated at the study clinic. This is viewed as a benefit because they save time and yet still get a better service while in the study. The study findings are not just relevant to understanding the motivations and experiences in participating in AMP study. The findings shed light on what may be a setback in the intersection of health care and health research. If potential participants rightly or wrongly believe that access to normal care, information or treatment can be easily accessed through research participation, then something is wrong with health services delivery and provision.
Andisen and Newman's concept of enabling factors was also observed in this study where he states personnel friendliness as one of the factors facilitating participation. It was noted that being welcomed and feeling welcomed placed a role for some of the participants to enrol and remain in the study. When they feel welcomed, they no longer view coming to the clinic as a burden but rather, they look forward to it. This helps the participants develop trust in the personnel as they feel free to talk to them about anything.

Financial benefits
In addition, participants are motivated by the transport money they are given knowing that they will make savings and sustain their lives which in turn improves their socioeconomic status. Besides not having to pay for the drugs that are being tried out in the study or receiving free treatment when they fall sick as was a finding by SABCS 2019 article on clinical trials, some participants reported the stipend they are given in the study as a study benefit. The stipend provides a platform of financial independence for some participants. With that, they plan on how to use their money according to their present needs thereby keeping them motivated to continue participating in the study and to enrol. Some openly said the main reason they enrolled in the study was that they heard there was money given as stipend which they felt they would benefit from it by participating.

Willingness to help their society
The perceptions and experiences of women taking part in HIV prevention trials were explored in Soweto, South Africa whereby the central finding was that the participants felt the sense of empowerment in spite of their being embedded in a culture that has come to fear, deny, or ignore AIDS [12]. This was also reported during this study where participants joined the AMP study just to willingly help the society in coming up with scientifically proven interventions to end the epidemic. The participants indicated that by volunteering to take part in the study, this will assist Malawi to have evidence based interventions to fight the virus and they will feel proud to have been part of the drive.
When enrolling in the study, the participants are clearly told that there will be no direct benefit to them since being a trial, they are only trying to see if the drip can be effective in preventing the transmission of HIV to those on it. Being aware of that, some enrolled with hope that they will be given the active drip while others enrolled because of a longterm goal of wanting to be a part of something that will help other people in future if proven effective. In the end, the satisfaction came in knowing that they played a role in other people's health.

Experiences of participants in the HIV Prevention clinical trial.
From the responses of the participants, the experiences are grouped into the positive experiences, which can be looked at benefits of being in the study as well as the challenges they experienced while in the study. A link was observed between the benefits experienced, and their ability to adhere to study procedures and visits.

Positive experiences
As stated under health benefits as a motivator to study participation, knowing one's status was one of the positive experiences by the participants. They therefore looked to the next visit when they would be tested and depending on the results, they would either go home knowing that everything that they were tested for is fine or knowing that whatever they were diagnosed with has been treated and they will get better. Even for those who were informed of the study by friends who had enrolled before them, highlighted that they were encouraged by the good health their friends had and upon enrolling, were encouraged to know that their health will be monitored. Knowing their status, participants were encouraged to continue practicing safe behaviours such as maintaining one sexual partner in order to maintain their HIV negative status.
Beyond knowing their status, they felt empowered because through the study their knowledge of HIV was improved. This meant that they now have a better idea of how to prevent HIV as well as how it is transmitted. Most participants interviewed reported that before the study, they did not know that having multiple sexual partners put them at a higher risk of contracting HIV or that having unprotected sex also puts them at risk even for those who had one sexual partner. From what they learnt in the study, they were later on able to decide to have one sexual partner but still use condoms to increase their chances of preventing HIV. Participating in the clinical trial therefore made the participants feel that they have more control over their health which led to a more positive outlook and better quality of life.

Negative experiences
Fear that the drug under trial (VRC01) may have side effects, especially related to child birth since they were not allowed to enrol if they are pregnant, breastfeeding, or if they had plans of having children within a space of two years from the time of enrolment.
Beyond that, they were required to be on a family planning method. The strictness brought about worries that they might have troubles conceiving after the study or that if they fell pregnant while in the study, there would be some complications.
Community stigma related to study participation came up from almost all those interviewed. They described that once people in the community learn of a person's study participation, they are told negative things to discourage their continued participation. In the communities, people have different views of research. Some think of research as being a satanic activity and they try to disassociate themselves with it while others think it is a scheme by the researchers to steal blood from the participants through the samples that are collected. However, regardless of what they were told, most participants still decided to continue taking part in the study because they had never experienced what they hear or heard of anyone in the study complain about the things the community described, and because they wanted to experience what was said for themselves and not just getting influenced by other people.
Decision making as to whether to take part in the AMP study or not was seen to have been made over other personal opportunities like getting married or being in good terms with relatives because they were mostly discouraging. The need to protect themselves and access to the different services in the study was seen as of greater importance compared to the community stigma, anticipated risk and discouragements from families and friends they experienced while taking part in the study.

Study limitations
All the participants were recruited within a period of two months. The participants who were interviewed for this study were those who came between those months. This implied that those who came before or after the specified months were not given a chance to participate, limiting the range of responses we could have probably attained if it was done over a longer period of time.
The conduct of the study was dependent on participants' AMP study visit schedules, therefore we had to wait for the participants to report to the clinic on their scheduled dates. This meant that those who were unable to take part in the interview on the day they reported for their clinic visit did not have a chance to come in whenever they felt able.

Conclusion
This study has shown that participants in the AMP study enrolled in the study first for personal benefitshealth, financialthen, for the desire to have taken part in something that will help other people in futurefor the greater good. When their expectations are met through what they experience in the study, the chances of them adhering to the study visits and procedures are high. Even for those who did not have any expectations prior to the study, feeling welcomed and being able to open up to the study staff encouraged their continued participation. In the end, this outweighed the negative comments made by the people in their communities or their friends, which is something almost all the participants who were interviewed mentioned to have experienced UNC project needs to continue providing other health services to the participants as this is promoting participation as well. Furthermore, the provision of transport money is encouraging participants to attend the clinic as per schedule.

Acknowledgements
My sincere gratitude goes to the following individuals: • My supervisor, Professor Adamson S. Muula for his hard work in taking me through my research.
• My dear husband Patrick Mbulaje for his continued support throughout the research period.
• The Management of UNC Project for granting me permission to conduct the study within the project.
• To Dr Agatha Bula and Annie Thom, thank you for your endless support.
• All my work colleagues and friends for their support and encouragement.

Declaration Confirming the Absence of Any Conflict Of Interest
I Ruth Holla, confirm that I do not have any conflict of interest in connection to the article submitted. A conflict of interest may arise in particular as a result of economic interests, political or national affinities, family and emotional ties, or any other relevant connection or shared interest.

Funding for The Study
No funding was received for this study. All the expenses were met by the researcher.  Un-employed 8