Care in HIV drug trial closure: perspectives of research participants and staff in Uganda

Background: After three decades, Human Immunodeficiency Virus (HIV) continues to pose significant threats globally. The efforts to curb the HIV epidemic have required investment in research, with clinical trials being a major focus, to develop HIV prevention, treatment, and cure interventions. A large portion of such research has been undertaken within low income settings, due to the high burden of HIV and the availability of willing volunteers within this setting. HIV research calls for the implementation of ethical research practice which is informed by policy guidelines. However, current policies are largely informed by inputs from high income countries, and lack the voices of those closely involved in research implementation. In order to contribute to ethics policy development in HIV research, it is essential to involve different stakeholders by exploring their experiences/views on the issue. Existing research in this field has mainly explored experience of recruitment and trial conduct, while very little has been done on trial closure, indicating a significant evidence gap worth exploring. This research therefore sought to illuminate, explore and understand the significant issues regarding the care of HIV positive drug trial participants during closure of HIV clinical trials, within a low income setting, specifically, Uganda. Study aim: The study aimed to explore how care is perceived and enacted in HIV drug trial closure in Uganda, by addressing the following specific objectives: 1. From the perspective of research participants and research staff, to explore the views, opinions and understandings of the ethical/legal/moral post-trial obligations in HIV drug trials. 2. From the perspective of research staff, to explore the experiences, practices and processes related to care for HIV drug post-trial participants in a low income setting. 3. From the perspective of research participants, to explore the experiences of care at trial closure. 4. From the perspective of research participants, to explore the experiences of transitioning from HIV research to care/community. Methodology: The study adopted an interpretive-constructivist approach, and employed a social constructivist grounded theory methodology. The study included a total of 21 trial participants and 22 research staff from three different HIV drug trials, in two Ugandan research institutions. In addition, relevant ethical documents were reviewed from two of the included trials. Data collection and analysis followed the principles of grounded theory, with data collection and preliminary analysis being undertaken concurrently, and earlier data informing subsequent data collection. Data collection strategies included individual interviews, focus group discussions, and key informant interviews. Data was collected over a period of 10 months, from October 2014 to August, 2015. NVivo10 software was used to manage the data. Ethical approval was received from the University of Nottingham UK and The AIDS Support Organization (TASO) Uganda, Research Ethics Committees (RECs). The study was registered with the Uganda National Council for Science and Technology (UNCST), as SS 3608. Permission to conduct the research was granted by the respective research institutions, and written informed consent was received from all respondents. Findings: The findings showed that trial closure was often stressful for HIV positive participants in Uganda, and often resulted in negative psychological, socio-economic and health impacts. The negative effects mainly resulted from being stopped from accessing research related health care, which was of a significantly higher quality, and the inability to find alternative care to match the research standards. The main concerns which arose during the transition process of participants from HIV drug trials to usual care facilities include: the loss of the quality care and valued relationships in research, the need to find and link to alternative care facilities, the need to meet the increased financial needs, and worries about the effects/outcomes of research participation. These concerns demanded a range of additional care and supportive strategies from researchers (and other stakeholders). A conceptual model, the model of ‘Facilitated Transition’ was developed, which summarises the findings of this research and provides a diagrammatic representation of the research findings, showing the links and relationships between the different elements. The research established that the transition of HIV positive trial participants from research to usual care facilities is a process, which appears to consist of three overlapping phases. These phases include: The pre-closure phase which represents events occurring before the actual trial closure but that underpin post-trial care, the trial closure phase which is the active phase of the closure, in which trial participants are prepared and exited from the trials, and the post-trial phase which represents the events occurring after trial participants have been linked to post-trial care facilities until 12 months later. These phases are demarcated by specific time points, which reflect how the transition process evolves, proceeds and concludes. At the various phases of the process, specific concerns (care needs) arise, being influenced by the participants’ previous care experiences and perceptions, plus their health and socio-economic positions. Specific actions are required to proactively facilitate trial participants during these phases. These actions are underpinned by the perceived ethical and moral responsibilities of the researchers, and are principally aimed at establishing a continuum of HIV care and treatment after trial closure, promoting positive care experiences for trial participants during the transition, and enabling the settlement and adaptation of trial participants to care in the public healthcare system. Conclusions: This is the first known study to investigate perspectives on post-trial care among HIV positive trial participants in a low income setting, from those closely engaged in the research process. This study has provided novel contributions in the area of HIV research ethics and post-trial care in general. The study has established that trial closure involving HIV positive participants raises significant ethical, moral and practical concerns in the Ugandan context. The findings further demonstrated that current post-trial care practice does not meet all the care needs of the HIV positive trial participants. Existing ethical recommendations on post-trial care place an emphasis on the need to ensure access to trial drugs and provision of trial results, where as less attention is given to other important aspects, as revealed in this research. To meet the post-trial care needs of HIV positive participants in Uganda, a comprehensive trial closure strategy is required. In addition to the already existing aspects of post-trial care, the new strategy should aim to: (i) address the financial needs of trial participants through financial assessment, support and empowerment, (ii) provide practical support during linkage to post-trial care, and (iii) offer post-trial follow-up to monitor and support the participants. Implementing these recommendations may require involvement of various stakeholders, including researchers, ethics authorities, research funders and donors, public healthcare workers, families, trial participants, and the community. Recommendations for future research: Further research is required to ascertain the rates of linkage to care, and to assess the health outcomes of post-trial participants following trial exit. In addition, a study to target the views of other stakeholders, such as the public healthcare facility workers, the family, and ethics authorities on post-trial care may be essential to understand better the ways in which to support HIV positive trial participants in Uganda. Furthermore, a longitudinal prospective study on a larger sample is required to test the model proposed in this research. And finally, there is need to deliberate more on the ethical and moral implications of financial benefits in HIV research involving HIV positive participants in a low income setting

Care in HIV drug trial closure: perspectives of research participants and staff in Uganda

Background: After three decades, Human Immunodeficiency Virus (HIV) continues to pose significant threats globally. The efforts to curb the HIV epidemic have required investment in research, with clinical trials being a major focus, to develop HIV prevention, treatment, and cure interventions. A large portion of such research has been undertaken within low income settings, due to the high burden of HIV and the availability of willing volunteers within this setting. HIV research calls for the implementation of ethical research practice which is informed by policy guidelines. However, current policies are largely informed by inputs from high income countries, and lack the voices of those closely involved in research implementation. In order to contribute to ethics policy development in HIV research, it is essential to involve different stakeholders by exploring their experiences/views on the issue. Existing research in this field has mainly explored experience of recruitment and trial conduct, while very little has been done on trial closure, indicating a significant evidence gap worth exploring. This research therefore sought to illuminate, explore and understand the significant issues regarding the care of HIV positive drug trial participants during closure of HIV clinical trials, within a low income setting, specifically, Uganda. Study aim: The study aimed to explore how care is perceived and enacted in HIV drug trial closure in Uganda, by addressing the following specific objectives: 1. From the perspective of research participants and research staff, to explore the views, opinions and understandings of the ethical/legal/moral post-trial obligations in HIV drug trials. 2. From the perspective of research staff, to explore the experiences, practices and processes related to care for HIV drug post-trial participants in a low income setting. 3. From the perspective of research participants, to explore the experiences of care at trial closure. 4. From the perspective of research participants, to explore the experiences of transitioning from HIV research to care/community. Methodology: The study adopted an interpretive-constructivist approach, and employed a social constructivist grounded theory methodology. The study included a total of 21 trial participants and 22 research staff from three different HIV drug trials, in two Ugandan research institutions. In addition, relevant ethical documents were reviewed from two of the included trials. Data collection and analysis followed the principles of grounded theory, with data collection and preliminary analysis being undertaken concurrently, and earlier data informing subsequent data collection. Data collection strategies included individual interviews, focus group discussions, and key informant interviews. Data was collected over a period of 10 months, from October 2014 to August, 2015. NVivo10 software was used to manage the data. Ethical approval was received from the University of Nottingham UK and The AIDS Support Organization (TASO) Uganda, Research Ethics Committees (RECs). The study was registered with the Uganda National Council for Science and Technology (UNCST), as SS 3608. Permission to conduct the research was granted by the respective research institutions, and written informed consent was received from all respondents. Findings: The findings showed that trial closure was often stressful for HIV positive participants in Uganda, and often resulted in negative psychological, socio-economic and health impacts. The negative effects mainly resulted from being stopped from accessing research related health care, which was of a significantly higher quality, and the inability to find alternative care to match the research standards. The main concerns which arose during the transition process of participants from HIV drug trials to usual care facilities include: the loss of the quality care and valued relationships in research, the need to find and link to alternative care facilities, the need to meet the increased financial needs, and worries about the effects/outcomes of research participation. These concerns demanded a range of additional care and supportive strategies from researchers (and other stakeholders). A conceptual model, the model of ‘Facilitated Transition’ was developed, which summarises the findings of this research and provides a diagrammatic representation of the research findings, showing the links and relationships between the different elements. The research established that the transition of HIV positive trial participants from research to usual care facilities is a process, which appears to consist of three overlapping phases. These phases include: The pre-closure phase which represents events occurring before the actual trial closure but that underpin post-trial care, the trial closure phase which is the active phase of the closure, in which trial participants are prepared and exited from the trials, and the post-trial phase which represents the events occurring after trial participants have been linked to post-trial care facilities until 12 months later. These phases are demarcated by specific time points, which reflect how the transition process evolves, proceeds and concludes. At the various phases of the process, specific concerns (care needs) arise, being influenced by the participants’ previous care experiences and perceptions, plus their health and socio-economic positions. Specific actions are required to proactively facilitate trial participants during these phases. These actions are underpinned by the perceived ethical and moral responsibilities of the researchers, and are principally aimed at establishing a continuum of HIV care and treatment after trial closure, promoting positive care experiences for trial participants during the transition, and enabling the settlement and adaptation of trial participants to care in the public healthcare system. Conclusions: This is the first known study to investigate perspectives on post-trial care among HIV positive trial participants in a low income setting, from those closely engaged in the research process. This study has provided novel contributions in the area of HIV research ethics and post-trial care in general. The study has established that trial closure involving HIV positive participants raises significant ethical, moral and practical concerns in the Ugandan context. The findings further demonstrated that current post-trial care practice does not meet all the care needs of the HIV positive trial participants. Existing ethical recommendations on post-trial care place an emphasis on the need to ensure access to trial drugs and provision of trial results, where as less attention is given to other important aspects, as revealed in this research. To meet the post-trial care needs of HIV positive participants in Uganda, a comprehensive trial closure strategy is required. In addition to the already existing aspects of post-trial care, the new strategy should aim to: (i) address the financial needs of trial participants through financial assessment, support and empowerment, (ii) provide practical support during linkage to post-trial care, and (iii) offer post-trial follow-up to monitor and support the participants. Implementing these recommendations may require involvement of various stakeholders, including researchers, ethics authorities, research funders and donors, public healthcare workers, families, trial participants, and the community. Recommendations for future research: Further research is required to ascertain the rates of linkage to care, and to assess the health outcomes of post-trial participants following trial exit. In addition, a study to target the views of other stakeholders, such as the public healthcare facility workers, the family, and ethics authorities on post-trial care may be essential to understand better the ways in which to support HIV positive trial participants in Uganda. Furthermore, a longitudinal prospective study on a larger sample is required to test the model proposed in this research. And finally, there is need to deliberate more on the ethical and moral implications of financial benefits in HIV research involving HIV positive participants in a low income setting

Moving to another world: understanding the impact of clinical trial closure on research participants living with HIV in Uganda

Despite an increasing need for clinical trials involving people living with HIV (PLWH), little is known about how PLWH experience trial closure, particularly in low-income countries, where the majority of trials take place. We sought to explore the impact of trial closure on PLWH in Uganda. This was an interpretive, grounded theory study using in-depth interviews, conducted between October 2014 and August 2015. Adult participants (N = 23) from 3 trials were included. The findings indicated that trial closure was represented as “moving to another world” and was an emotional transition, linked to a loss of quality care in the research environment, the need to find alternative health facilities, fear of experiencing unwanted side effects, a desire to receive trial feedback, and difficulties linking to posttrial care. We concluded that PLWH leaving trials in a resource-limited setting required holistic care to facilitate their transition back to “usual care.

Facilitated transition in HIV drug trial closure: A conceptual model for HIV post-trial care

Within the HIV clinical trial field, there are gaps in existing ethical regulations in relation to post-trial care. There is need to develop post-trial care guidelines that are flexible and sensitive to local contexts and to the specific needs of different groups of participants, particularly in low income contexts. Evidence regarding HIV trial closure and post-trial care is required to underpin the development of appropriate policies in this area. This article reports research from Uganda that develops a new model of ‘Facilitated Transition’ to conceptualize the transition process of HIV positive trial participants from ‘research’ to ‘usual care’ health facilities after trial conclusion. This was a qualitative grounded theory study that included 21 adult HIV positive post-trial participants and 22 research staff, undertaken between October 2014 and August 2015. The findings showed that trial closure is a complex process for HIV positive participants which includes three phases: the pre-closure, trial-closure, and post-trial phases. The model highlights a range of different needs of research participants and suggests specific and person-centred interventions that can be delivered at different phases with the aim of improving health outcomes and experiences for trial participants in low income settings during trial closure. Further research needs to be done to verify the model in other contexts and for other conditions

Ethical and practical considerations in HIV drug trial closure: perspectives of research staff in Uganda

There is a gap in evidence regarding how research trial closure processes are managed to ensure continuity of HIV care for HIV positive participants following trial closure within low income settings. This research aimed to establish how research staff in Uganda understood and practised post-trial care for HIV positive trial participants. A grounded theory study was conducted using in-depth individual interviews and focus group discussions with 22 research staff from three different trials in Uganda. The results indicated that researchers engaged in three main activities to support trial participants, including: (i) preparing for post-trial care, which included instituting trial closure guidelines, planning necessary resources, and informing trial participants about post-trial care; (ii) facilitating participants during trial exit by engaging in psychological and practical support activities and (iii) providing follow up care and support for participants after trial exit, to respond to the needs of trial participants which often arose after trial exit. This study established a need for a holistic approach to post-trial-care of HIV positive trial participants in Uganda, and the need to engage multiple stakeholders including ethics authorities

Participant views and experiences of participating in HIV research in sub-Saharan Africa: a qualitative systematic review

BACKGROUND: Human immunodeficiency virus clinical trials are increasingly being conducted in sub-Saharan Africa. There is a tension between the pressure to increase levels of research participation and the need to ensure informed consent and protection of participants' rights. Researchers need to be aware of the particular ethical issues that underpin Human immunodeficiency virus research conduct in low income settings. This necessitates hearing from those who have participated in research and who have direct experience of the research process.OBJECTIVES: This review aimed to synthesize and present the best available evidence in relation to Human immunodeficiency virus research participation in sub-Saharan Africa, based on the views and experiences of research participants.INCLUSION CRITERIA:TYPES OF PARTICIPANTS: The review included studies whose participants were current or former adult Human immunodeficiency virus research participants from sub-Saharan African countries.PHENOMENON OF INTEREST: Views, experiences, attitudes, understandings, perceptions and perspectives of Human immunodeficiency virus research participants in sub-Saharan Africa. Types of studies: This review considered studies that focused on qualitative data, including, but not limited to, designs such as phenomenology, ethnography, grounded theory, action research and feminist research.SEARCH STRATEGY: A three-step search strategy was utilized. Seven databases (CINAHL, Ovid MEDLINE (R) 1946, ASSIA, PsychInfo, Web of Science, EMBASE, and African Index Medicus) were searched with no limitation to years of publication, followed by hand searching of reference lists. Only studies published in the English language were considered.METHODOLOGICAL QUALITY: Methodological quality was assessed using the Qualitative Assessment and Review Instrument developed by the Joanna Briggs Institute.DATA EXTRACTION: Qualitative findings were extracted using the Joanna Briggs Institute Qualitative Assessment and Review Instrument.DATA SYNTHESIS: Qualitative research findings were pooled using a pragmatic meta-aggregative approach and the Joanna Briggs Institute Qualitative Assessment and Review Instrument software.RESULTS: Twenty-one studies were included in the review. One hundred and thirty-six findings were extracted from included studies and clustered into 14 categories based on similarities in meaning. These were further synthesized into five synthesized findings, set out below; i) Individuals are motivated to participate in Human immunodeficiency virus research due to a range of perceived benefits for themselves and others. ii) Participation in research can be associated with considerable fear and uncertainty. iii) Participation in Human immunodeficiency virus research is strongly influenced by social relationships (e.g. support or disapproval of family or friends) and social-economic and domestic factors (such as time or finances). iv). The meanings of research programs and processes are constructed within a context of existing lay beliefs, experiences and social relations associated with Human immunodeficiency virus and biomedical interventions in general. This means that local people may understand research and its processes very differently to health professionals. v) Participants' research experiences and their continued participation in Human immunodeficiency virus research are influenced by the research clinic context and the nature of their interactions with research staff.CONCLUSIONS: Individuals are generally willing to participate in Human immunodeficiency virus research. However their understanding of the process can be limited, and the experience may may cause anxiety or have negative consequences. Furthermore longer-term participation may become problematic due to socio-economic pressure or social commitments.IMPLICATIONS FOR PRACTICE: The review suggests a need to develop better ways to explain research processes and to support participants, when/if they encounter problems. There is also a need to engage better with communities in order to educate them about HIV research programs.IMPLICATIONS FOR RESEARCH: All the included studies focused on experiences around research enrolment and participation (retention); however there is a complete evidence gap on experiences of trial closure

The views and experiences of nurses and midwives in the provision and management of routine (provider initiated) HIV testing: a systematic review of qualitative evidence

Background: Global progress towards HIV prevention and care is contingent upon increasing the number of those aware of their status through HIV testing. Provider-initiated HIV testing and counseling is recommended globally as a strategy to enhance uptake of HIV testing and is primarily conducted by nurses and midwives. Research shows that provider-initiated HIV testing and counseling implementation is sub-optimal. The reasons for this are unclear.Objectives: The review aimed to explore nurses' and midwives' views and experiences of the provision and management of provider-initiated HIV testing and counseling.Inclusion criteria Types of participants: All cadres of nurses and midwives were considered, including those who undertake routine HIV testing as part of a diverse role and those who are specifically trained as HIV counselors.Types of phenomenon of interest: The review sought to understand the views and experiences of the provision and management of provider-initiated HIV testing and counseling (including perceptions, opinions, beliefs, practices and strategies related to HIV testing and its implementation in practice).Context: The review included only provider-initiated HIV testing and counseling. It excluded all other models of HIV testing. The review included all countries and all healthcare settings.Types of studies: This review considered all forms of qualitative study design and methodology. Qualitative elements of a mixed method study were included if they were presented separately within the publication.Search strategy: A three-step search strategy was utilized. Eight databases were searched for papers published from 1996 to October 2014, followed by hand searching of reference lists. Only studies published in the English language were considered.Methodological quality: Methodological quality was assessed using the Qualitative Assessment and Review Instrument developed by the Joanna Briggs Institute.Data extraction: Qualitative findings were extracted using the Joanna Briggs Institute Qualitative Assessment and Review Instrument.Data synthesis: Qualitative research findings were pooled using a pragmatic meta-aggregative approach and the Joanna Briggs Institute Qualitative Assessment and Review Instrument software.Results: This review included 21 publications from 18 research studies, representing a wide range of countries and healthcare settings. There were 245 findings which were aggregated into 12 categories and five synthesized findings:1. Nurses/midwives are supportive of provider-initiated HIV testing and counseling if it is perceived to enhance patient care and to align with perceived professional roles.2. Nurses'/midwives' ability to perform provider-initiated HIV testing and counseling well requires an appropriate infrastructure and adequate human and material resources.3. At the organizational level, nurses'/midwives' engagement with provider-initiated HIV testing and counseling is facilitated by an inclusive management structure, alongside the provision of ongoing training and clinical supervision. Provider-initiated HIV testing and counseling is hindered by difficulties in fitting it into existing workloads and routines.4. Nurses/midwives perceive that good quality care in provider-initiated HIV testing and counseling involves finding a balance between public health needs and individual patient needs. Good care requires time and the ability to apply a patient centred approach.5. The emotional work involved in provider-initiated HIV testing and counseling can be stressful. Nurses/Midwives may require support to deal with complex moral and ethical issues.Conclusions: This review shows that provider-initiated HIV testing and counseling is supported by nurses/midwives who strive to implement it according to principles of good care and a patient centered approach. Nurses/midwives face multiple operational, infra-structural, resource and ethical challenges in the implementation of provider-initiated HIV testing and counseling.Implications for practice: The implementation process for provider-initiated HIV testing and counseling would benefit from using a quality improvement framework. Nurses/midwives undertaking provider-initiated HIV testing and counseling require management support, ongoing training and adequate infrastructure/resources. Additional guidance is required on legal/ethical issues in testing of children and in third party disclosure.Implications for research: Operational research is required to determine an optimal skill mix and optimal methods of integrating provider-initiated HIV testing and counseling into existing work routines

The practice of pilot/feasibility studies in informing the conduct of HIV related clinical trials in sub-Saharan Africa: A scoping review

Introduction: Pilot/feasibility studies represent a fundamental phase of the research process and play a vital role in the preliminary planning of a full size HIV clinical trial. Published HIV clinical trial protocols were reviewed to establish the extent to which the proposed HIV clinical trials are informed by a prior pilot/feasibility study. Methods: The JBI methodology for scoping reviews was followed. Six databases were systematically searched to identify articles for inclusion. Results: Thirty two (32) published HIV study protocols were included. Articles were in the English language and were published in the past 10 years (2011–2020). The review results showed that the majority of HIV-related clinical trials in sub-Saharan Africa were not informed by pilot/feasibility studies. The results further indicated that the number of HIV clinical trials informed by a pilot/feasibility study have been on the increase in the 8 years’ period since 2012, a trend that indicates positive uptake of pilot studies in HIV related studies. A few select countries (South Africa, Uganda, Zimbabwe, Malawi and Kenya) comprised more than 70% of all clinical trials that were informed by a pilot/feasibility study, conducted in sub Saharan Africa. Conclusions: Although there is an increasing interest among researchers to integrate pilot/feasibility studies in HIV related research, limited countries in sub-Saharan Africa appear to have embraced this trend. Strategies that can motivate researchers to engage in a culture of incorporating pilot/feasibility studies in HIV related research should be implemented

Emotional Reaction to the First Dose of COVID-19 Vaccine: Postvaccination Decline in Anxiety and Stress among Anxious Individuals and Increase among Individuals with Normal Prevaccination Anxiety Levels

Although vaccination has been adopted by the WHO to limit worldwide transmission of COVID-19, people’s worries about COVID-19 vaccines may suppress their desire for vaccination despite vaccine availability. This study aimed to investigate anxiety and stress symptoms among 250 Jordanians (mean age = 43.18 ± 6.34 years, 72% females) who received their first vaccine dose. The respondents completed the anxiety and stress subscales of the Depression Anxiety and Stress scale 21 (DASS-21) before and after vaccination. The respondents expressed more moderate–severe levels of stress before than after vaccination (20.8% and 13.2%, respectively). Meanwhile, 37.2% and 45.2% of the respondents expressed moderate–severe anxiety before and after vaccination, respectively. Wilcoxon signed-rank test revealed that the drop in the level of stress from before- (median (IQR) = 5 (1–8)) to after vaccination (median (IQR) = 3 (1–7)) was statistically significant (z = −3.81, p = 0.001, r = 0.17) while the increase in anxiety was not. Anxiety significantly dropped postvaccination among individuals experiencing mild to severe anxiety before vaccination. Similarly, stress and anxiety significantly increased among individuals expressing normal anxiety before vaccination (z = −3.57 and −8.24, p values = 0.001, r = 0.16 and 0.37, respectively). Age positively correlated with postvaccination anxiety among respondents with mild prevaccination anxiety, and it negatively correlated with the prevaccination level of stress in the normal-anxiety group. Gender, marital status, respondents’ level of education, and history of COVID-19 infection had no significant correlation with anxiety or stress at either point of measurement. Overcoming their hesitancy to receive COVID-19 vaccines, individuals with normal levels of anxiety experienced a rise in their distress symptoms following immunization. On the contrary, vaccination seemed to desensitize anxious individuals. Policymakers need to formulate a population-specific plan to increase vaccine preparedness and promote psychological well-being over all during the pandemic