Participant satisfaction with clinical trial experience and post-trial transitioning to HIV care in Kenya

Abstract

We conducted an exploratory analysis of former HIV Prevention Trials Network 052 (HPTN 052) clinical trial participants in 2016 to assess their (1) satisfaction with the HPTN 052 clinical trial care and treatment, and reasons for joining the trial; and (2) perspectives about the post-trial transition to public HIV care centers. Quantitative data showed that, of the 70 survey participants, 94.3% (n = 66) reported being very satisfied with the care and treatment they received while participating in the clinical trial and 51.4% (n = 36) reported they joined the study because they would receive information to improve their own or their partner’s health. Qualitative data (five in-depth interviews and two focus group discussions) analysis revealed the following themes: transition experiences; perceived superior clinical trial care; study benefits not offered at public HIV care centers; and the public HIV care centers’ indifference to the uninfected partner. For some HPTN 052 participants, transition to HIV care clinics was disappointing. Clinical trial investigators and local Institutional Review Boards should consider the need for safeguards and oversight of post-trial health care for trial participants after the trial ends, especially in resource-constrained settings, to avoid negative health outcomes.

Keywords

Transition clinical trial HIV Prevention Trials Network 052 discordant couples Kenya NCT00074581 post-trial access ethics

Introduction

Patient satisfaction is becoming an important measure in health care systems, including clinical trials.¹ Measuring participant satisfaction in a clinical trial can be useful to inform, and potentially modify, clinical services, as needed.^2,3 Persons with a health condition, such as HIV, who participate in a clinical trial often find themselves returning to the general health care system after their time in the trial is completed. However, the post-trial period is a vulnerable time for some persons with HIV infection;⁴ access to the trial intervention or the standard of care through the health care system is critical for participants with HIV living in resource-constrained settings.⁵ A qualitative study of HIV Prevention Trials Network (HPTN) investigators and staff found that post-clinical trial access to interventions requires concerted efforts, involvement of stakeholders, and follow-up.⁶ It has been suggested that regulators and interested stakeholders consider revising guidelines to recognize that some participants may lack access to health care and may need targeted additional benefits for their study participation.⁷ It is relevant to note that qualitative studies of persons in public HIV care in sub-Saharan Africa have reported unpleasant treatment by providers, including the clinic staff or providers being rude and/or rejecting.⁸ These experiences caused feelings of hurt, anger, and humiliation.⁹

A multi-site clinical trial, HPTN 052, completed in 2015, aimed to compare the rates of HIV infection among partners of HIV-infected participants in two study arms. Results showed that HIV transmission was reduced by 93% when the HIV-infected partner started antiretroviral therapy (ART) before their immune system became severely compromised.^10,11 Exploring the HPTN 052 clinical trial participants’ satisfaction with the study, and their experiences at the point when they entered a public HIV care center, may inform the discussion of improvements in the oversight of former clinical trial participants in post-trial responsibility documents and frameworks, such as the ones produced by the Multi-Regional Clinical Trials (MRCT) Center.^12,13 The present study is an exploratory analysis of a larger study that used a survey, in-depth interviews (IDIs), and focus group discussions (FGDs) to assess various attitudes about HIV discordancy among members of discordant couples. About a third of the members in that larger study had been participants in the HPTN 052 clinical trial. Objectives of this exploratory analysis that focused on the HPTN 052 participants were to assess: (1) satisfaction with the HPTN 052 clinical trial, and reasons for joining the trial and (2) perspectives about the post-trial transition to public HIV care centers.

Methods

Study location and participants

Asembo and Karemo regions within Siaya County, Kenya served as the study location. Participants in the overall study, conducted in 2016, were either recruited through the HPTN 052 clinical trial, which followed discordant couples for five years,¹⁰ or from the President’s Emergency Plan for AIDS Relief-funded HIV care clinic support groups. Henceforth, we will focus on the persons who had participated in the HPTN 052 clinical trial and had transitioned to public HIV care centers. These persons, who had provided consent to be re-contacted, were contacted by the study staff who conducted follow-up and referral activities for the main clinical trial. The staff had existing relationships with these participants.

Design

The study used mixed methods. The inclusion criteria were age ≥18 years, member of a discordant couple, resident of Asembo or Karemo, and willing to give informed consent to study participation. Two survey questions related to participation in the trial and were: ‘What made you interested in joining the HPTN 052 study?’ and ‘How satisfied were you with the care and treatment you received in the HPTN 052 Study?’. IDIs and FGDs lasted approximately 60 minutes and FGDs were comprised of 6–10 participants. Questions for both the IDIs and FGDs included the following: ‘Thinking about the referral process, how would you describe your experience?’; ‘Is there something you wish could have been done differently, and how would this be?’; ‘What are your thoughts regarding how you are being handled/treated at your current HIV care center’; ‘If you were in charge of transitioning participants from the study to health services outside the study, how would you handle it?’; and ‘What would you tell the study team if they were to conduct a similar activity in future?’. It is important to note that both members of the couple were not always able to participate in the survey, IDIs, or FGDs.

Transition procedure

The site planned a nine-month transition period for each participant prior to their last scheduled clinic visit to facilitate changeover to their preferred public HIV care center for continued care. Participants were presented with a list of facilities providing HIV comprehensive care centers that met the Kenya Ministry of Health (MoH) requirements. On their third to last visit, each participant shared their preferred referral facility and was given a referral/transfer letter in line with the Kenyan MoH guidelines. Study staff arranged to accompany them to their preferred facility to introduce them and confirm that their regimen was available there. Upon successful transfer and linkage to the public HIV care center, the study drug was withdrawn and participants were initiated on the public HIV care center regimen.

Ethics

Participants provided informed voluntary, verbal consent to participate in the present study following explanation of the study, its benefits and risks, and after having the opportunity to ask questions. The study protocol, consent forms, and data collection instruments were reviewed and approved by the KEMRI Scientific and Ethical Review Unit (#3098) and the United States Centers for Disease Control and Prevention. Survey, IDI, and FGD participants were reimbursed 500 Kenya shillings (equivalent to $5) for their transportation and given a bar of soap as a token of appreciation for their participation. The grant number for the original HPTN 052 clinical trial is 5-UM1-AI068619.

Analysis

Survey data were analyzed using simple frequencies (Stata 10, StataCorp, College Station, TX, USA). IDIs and FGDs were transcribed verbatim and translated from Dholuo or Swahili to English. A codebook was developed and Nvivo 10, a qualitative data analysis software, was used to organize the data according to questions from transcribed discussions and to code themes regarding transitioning from the clinical trial to a public HIV care center. A ‘grounded theory’ method was used for data analysis, an inductive approach where theory is generated from the data. Quotes provided were selected on the basis of their clear representation of the question responses and themes.

Results

Seventy members of discordant couples participated in the survey, five participated in an IDI, and 15 participated in two separate FGDs. Approximately half of the survey respondents and those who took part in the IDI and FGD were female. Nearly all were married and most had a low income (<5000 KSH or $50/month) (Table 1).

Table 1.

Characteristics of former HPTN 052 clinical trial participants who participated in the in-depth interviews, focus group discussions, and survey, Asembo and Karemo, Kenya, 2016.

	In-depth interviewsN = 5	Focus group discussionsN = 15^a	SurveyN = 70
Gender
Female	3 (60.0)	7 (46.7)	37 (52.9)
Male	2 (40.0)	8 (53.3)	33 (47.1)
Age (years)
18–29	1 (20.0)	5 (35.7)	5 (7.1)
30–39	1 (20.0)	5 (35.7)	12 (17.1)
40–49	0 (0.0)	1 (7.1)	24 (34.3)
50+	3 (60.0)	3 (21.4)	29 (41.4)
Highest level of education
Primary	2 (40.0)	12 (80.0)	44 (68.8)
Secondary/college/ university	3 (60.0)	3 (20.0)	20 (31.3)
Income
Less than or equal to 1000 KSH	0 (0.0)	1 (6.7)	20 (28.6)
1001–5000 KSH	4 (80.0)	9 (60.0)	36 (51.4)
5001–10,000 KSH	1 (20.0)	2 (13.3)	11 (15.7)
>10,000 KSH	0 (0.0)	3 (20.0)	3 (4.3)
Religion
Catholic	3 (60.0)	7 (46.7)	12 (17.1)
Protestant	2 (40.0)	8 (53.3)	47 (67.1)
Other	0 (0.0)	0 (0.0)	11 (15.7)
Currently working
No	–	–	33 (47.1)
Yes	–	–	37 (52.9)
Occupation
Fisherman/farm/ fish vendor	–	–	53 (75.7)
Other	–	–	17 (24.3)
Marital status
Single	0 (0.0)	0 (0.0)	7 (10.0)
Married	5 (100.0)	15 (100.0)	59 (84.3)
Once married/ divorced/separated/ widowed	0 (0.0)	0 (0.0)	4 (5.7)

HPTN 052: HIV Prevention Trials Network 052; KSH: Kenya shillings.

Note: All categories do not add to total due to missing values. The categories ‘currently working’ and ‘occupation’ were not collected for the in-depth interviews and focus group discussions.

^aTwo focus group discussions.

Quantitative

The majority of the 70 survey participants, 94.3% (n = 66), reported they were very satisfied with the care and treatment they received in the HPTN 052 clinical trial. Moreover, 51.4% (36/70) reported that they joined they study because they would receive information to improve their own or their partner’s health, 28.6% (20/70) to reduce the chance of transmission, and 20.0% (14/70) to receive healthcare for themselves or their partner.

Qualitative

Findings were categorized according to the six themes below (Table 2).

Table 2.

Themes based on in-depth interviews and focus group discussions with former HPTN 052 clinical trial participants, Asembo and Karemo, Kenya, 2016.

Themes

Clinical trial provided knowledge

The transition experiences

Perceived superior clinical trial care

Study benefits not offered at public HIV care center

Public HIV care center indifference to the uninfected partner

Suggestions for future transition improvements

HPTN 052: HIV Prevention Trials Network 052.

Note: In-depth interviews n = 5, two focus group discussions n = 15.

Clinical trial provided knowledge

Participants reported that they gained immense knowledge of HIV during the study participation period. They reported being taught skills and given assistance as well as acquiring coping mechanisms to deal with the challenges of stigma and discrimination. Former HPTN 052 participants reported being seen as knowledgeable and empowered persons who should provide ART advice and mentorship to others in the public HIV care center.

I am well treated and I am now regarded as one who is full of information that is important. I am urged to share this information with others that were not with us for the HPTN 052 study… We have been accepted as those with knowledge and are fit to educate others as we have been trained for the past five years. (FGD with male discordant partner)

I only want to say that the studies being done by KEMRI/CDC are creating awareness in the public and continue to help the lives of people. (IDI with male member of discordant couple)

Conversely, there was no mention of learning in the current public HIV care centers. It does not mean that educational efforts were not made in the public HIV care centers, it just was not mentioned. It is as though the learning stopped once the former HPTN 052 participants exited the study. Some former HPTN 052 participants wished for an extension of the study period for them to continue receiving education.

The transition experiences

There were mixed reactions to the transition from being a participant in the HPTN 052 study to receiving care at the public HIV care centers. Most felt confident in the transition process and that they were adequately prepared through open discussions with the study team. These discussions included the topics of referral site preference and study team assistance, specifically, introduction to the referral site health care workers at the first visit.

They informed us that they would be taking one person at a time to a place that is close to them (FGD with female member of discordant couple).

For some, they felt the psychological preparation from the study team on the expected difference in care was important in helping them cope with the challenges of transitioning to their new public HIV care center, however, the change was still hard to accept.

What happened is that the study staff prepared us psychologically though it was still quite shocking since we had been so familiarized with [clinical trials site]. It’s like we were children who were being spoon fed and so when you hear that you want to compete with other children you will not be comfortable. It wasn’t very easy but we had to go…. (FGD with female member of discordant couple)

People who were used to that place, truly those people are still crying. You hear some people who were transitioned to some health facilities say, ‘We don’t know why the study had to come to an end’. (IDI with female discordant couple)

Perceived superior clinical trial care

The HPTN 052 clinical trial care was perceived to be superior compared to the care provided by the public HIV care center. This was due to the seeming availability of more thorough clinicians, stable and secure supplies requisite for HIV care, and provision of other regular vital screenings.

Treatment at [clinical trials site] was the best. (IDI with female member of discordant couple)

In some instances, the clinical trial providers were seen to be more professional, accommodating, and readily accessible for consultations than those at the public HIV care center.

The people here [public HIV care centers] are just helpers; on the other side [clinical trials site] we were dealing with professionals. (IDI with male member of discordant partner)

Some participants also alluded to the fact that they felt they were treated with more respect and concern in the clinical trial study compared to their current public HIV care center.

Study benefits not offered at public HIV care center

Participants reported that they had been informed to expect disruptions of certain benefits offered at the clinical trial setting. Nonetheless, for some, this new reality made their transition difficult.

Yes they [study team] used to pick and drop us with a vehicle. Sometimes they would call us before even you prepare the breakfast…. People who were used to that place, truly those people are still crying… (IDI with female member of discordant couple)

Public HIV care centers’ perceived indifference to the uninfected partner

The participants also found the public HIV care center was less focused on their needs as discordant couples. This included lack of specific programs or activities for the uninfected partner or encouraging their involvement.

When you go [care center], you only find HIV-positive persons alone in the clinic; partners who are HIV-negative do not escort these people, what I mean is that they do not support them. (IDI with female member of discordant partner)

Dissatisfaction with the routine HIV care center after participation in the HPTN 052 clinical trial can be grouped into categories such as health infrastructure, transport and others (Table 3).

Table 3.

Former HPTN 052 clinical trial participants’ reasons for dissatisfaction with routine care at public HIV care centers after trial, Asembo and Karemo, 2016.

Suggestions for future transition improvements

Token of appreciation

Some participants recommended a financial send-off package which might include business capital to enable them to earn an income, help with building a house for those without proper housing, and assistance paying their children’s school fees as a form of appreciation for their voluntary efforts in the study.

Even if you are not working, there could be some money that you can use to start your small business. (IDI with a male member of discordant couple)

Additionally, some participants suggested that issuing a certificate of participation would serve to recognize them and reward their efforts.

Follow-up after transition

Another suggestion was to conduct follow-up visits to ensure successful linkage and continue regular home visits to monitor transition progress and adherence compliance. Although some participants took referral letters, their linkage was not ideal. It was reported that two persons found it so difficult that they opted to drop out of care, and subsequently lost their lives.

There are some people who were given referral forms but did not go for care and in the end they died. (IDI with male member of discordant couple)

Discussion

HIV affects 4.8% of married and cohabiting couples in Kenya.¹⁴ These couples have unique needs, and thus require attention and knowledge regarding disclosure, pregnancy planning, relationship concerns, and prevention for the uninfected partner. The HPTN 052 discordant couple clinical trial provided counseling for the couple, medication, and medical care. While there are definite benefits of participating in clinical trials for discordant couples, there are also drawbacks to consider, especially when it comes to continuing care after the study in resource-constrained settings.

Our study suggested that participating in the HPTN 052 clinical trial empowered participants with the skills to cope with their health conditions and gave them valuable HIV-related knowledge. This empowerment enabled them to handle the stigma and discrimination associated with being a member of a discordant couple, and enhanced their ability to disclose to their partner and maintain a healthy relationship. This kind of tailored care was important in the context of asymmetric power roles within the couple, and gender expectations that included married women having children.¹⁵ Clearly, there is a need for HIV-related knowledge, as 51.4% of persons responding to the survey question about why they joined the HPTN 052 clinical trial reported that it was because they would receive information to improve their or their partner’s health. As the end of the study approached and discussion of transition to a public HIV care center began, some participants reported feeling scared and worried, with some even reporting that they prayed that a new discordant couple program would begin. It seems that some may have felt that they would like to continue learning in the research setting as well as experiencing the supportive study environment.

Moreover, our results showed that many former HPTN 052 clinical trial participants perceived a higher quality of care in the HPTN 052 clinical trial compared to the public HIV care center. Participants may have experienced care at the public HIV care center relative to the HPTN 052 clinical trial as worse for various reasons. One reason is that Kenya’s health infrastructure is not well-developed. While Kenya has one doctor and 12 nurses and midwives per 10,000 people, the World Health Organization (WHO) recommends that Kenya should have nearly twice that number.¹⁶ As a result, there are long wait times for patients to see health care providers, plus many with HIV infection do not want to be seen at large government sponsored facilities¹⁷ where they can meet individuals they interact with within the larger community. Another reason may be that the knowledge that the HPTN 052 participants acquired from the clinical trial challenged the authority of the public health care providers and created tension. When there is limited time with the patient, the physician may feel frustrated having to explain why the routine is different in the public HIV center than it was in the clinical trial setting.¹⁸ Another potential reason why the public HIV care center may have been viewed as worse than the HPTN 052 clinical trial care is the lack of transport reimbursement and/or lunch at the visit, which the HPTN 052 participants were used to receiving. Relatedly, clinical trial staff are motivated to accommodate participants when possible (i.e. reminder calls) to increase participant retention. This is not the case with health care staff in public HIV care centers. Similar reasons have been discussed in the context of implementing post-trial access plans to HIV prevention research.⁶ Finally, the public HIV care center was perceived as indifferent to the uninfected partner. Former HPTN 052 participants in our study appreciated the study staff communication with both members of the discordant couple and felt it provided both members with the same information, which helped their relationship. Similarly, qualitative studies of HIV-infected young people in eastern Africa and South Africa highlighted the importance of including both members of a discordant couple in care and interventions.^15,19 There is general agreement on the need to move beyond the individual, and increase focus on couple-based HIV prevention and intervention strategies.^15,20–22

Therapeutic misconception may be a reason why some former HPTN 052 participants were dissatisfied with the HIV care center. Henderson defines therapeutic misconception as

…when individuals do not understand that the defining purpose of clinical research is to produce generalizable knowledge, regardless of whether the subjects enrolled in the trial may potentially benefit from the intervention under study or from other aspects of the clinical trial.²³

However, it seems the onus for conveying the understanding or providing an agreed-upon incentive is on the research investigators and staff who are working in developing countries. Global health inequalities must be at the forefront of the thought processes and decision making of regulators, investigators and staff. It is not enough to say the explanation was provided in the informed consent so the potential participants should understand and realize they may get no direct benefits from the study.²⁴ The participants may have been provided with many services they normally do not have access to in order to facilitate their retention. Investigators may want to consider whether clinical trials need to better manage participants’ expectations of study benefits²⁵ and perhaps consider how to empower the participant more broadly as the suggestions for compensation indicate.

Our exploratory analysis is subject to at least four limitations. First, the number of persons participating in the IDIs and FGDs was small. A larger sample size may have resulted in additional themes. Second, the duration between the end of the trial and the current data was over a year, thus there may be a possibility of recall bias. Third, we did not have quantitative post-trial data on medication regimens, adherence, viral loads, or deaths. Finally, this study was based at one site in Kenya, thus generalizations to other clinical trial sites cannot be made.

In conclusion, while participation in the HPTN 052 clinical trial offered participants many advantages, the same advantages were not always present at the public HIV care centers they were transitioned to after the clinical trial. This caused some feelings of disappointment among participants who were very satisfied with the care they received in the HPTN 052 clinical trial. The Medicines for Human Use Regulations 2004 indicates that the trial sponsor should offer details of ‘the plan for treatment or care of subjects once their participation in the trial has ended’ when applying for an Ethics Committee opinion.²⁶ There is growing emphasis on the obligations researchers and funders have to consider arrangements for post-trial care for participants.^27,28 Within this context, questions prompted by this exploratory analysis include: (1) What is the role of the principle investigator and the IRBs in ensuring continued high standards of care given that clinical trial standards of care are often superior to the country standard of care in resource-constrained settings? and (2) What can participants negotiate for, and from whom, in terms of their continuity of care? Moreover, the ethical question of whether the perceived superior level of care received during a clinical trial puts some participants at risk for dropping out of care after the trial is over, must be considered due to dissatisfaction with the post-trial public HIV care center care.⁶ Relatedly, it has been suggested that clinical trials consider using patient navigators during the transition period.⁴ It would be prudent to bring former, current, and potential clinical trial participants, as well as opinion leaders, into the discussion of relevant compensation for participants before the trial begins.

Data sharing

The data underlying this study are subject to ethical restriction and owned by the CDC. All data are available upon request, and data requests should be directed to the Centers for Disease Control and Prevention, NCHHSTP, DHAP, Epidemiology Branch at 1600 Clifton Rd, MS E-45, Atlanta, GA 30333. Please note that release of these data must be in accordance with the provisions of the Public Health Service Act (42 U.S.C. 242m(d)), requiring that the privacy of individuals who provide personal information be protected. In addition, the CDC/ATSDR Policy on Releasing and Sharing Data specifies that, in order to meet privacy requirements, CDC must ensure that confidential information is not disclosed.

Disclaimer

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

Footnotes

Acknowledgements

We extend appreciation to the HPTN 052 protocol team, and to all study participants. We also thank the study staff, especially Eucabeth Awuonda and Tereza Omoro, for their expert assistance in carrying out the study. This manuscript is published with the permission of the Director of KEMRI Center for Global Health Research.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the U.S. National Institutes of Health (grant number NCT00074581, 2007).

References

Pflugeisen

Rebar

Reedy

et al . Assessment of clinical trial participant patient satisfaction: A call to action. Trials 2016; 17: 483.

Verheggen

Nieman

Reerink

et al . Patient satisfaction with clinical trial participation. Int J Qual Health Care 1998; 10: 319–330.

Tangrea

Adrianza

Helsel

WE.

Patients' perceptions on participation in a cancer chemoprevention trial. Cancer Epidemiol Biomarkers Prev 1992; 1: 325–330.

Yehia

Long

Stearns

et al . Impact of transitioning from HIV clinical trials to routine medical care on clinical outcomes and patient perceptions. AIDS Care 2012; 24: 769–777.

Sofaer

Lewis

Davies

Forthcoming practical framework for ethics committees and researchers on post-trial access to the trial intervention and healthcare. J Med Ethics 2014; 40: 217–218.

Paul

Merritt

Sugarman

Implementing post-trial access plans for HIV prevention research. J Med Ethics 2018; 44: 354–358.

Dal-Re

Rid

Emanuel

et al . The potential exploitation of research participants in high income countries who lack access to health care. Br J Clin Pharmacol 2016; 81: 857–864.

Ondenge

Renju

Bonnington

et al . 'I am treated well if I adhere to my HIV medication': Putting patient–provider interactions in context through insights from qualitative research in five sub-Saharan African countries. Sex Transm Infect 2017; 93(3): e052973.

Ware

Wyatt

Geng

et al . Toward an understanding of disengagement from HIV treatment and care in sub-Saharan Africa: A qualitative study. PLoS Med 2013; 10: e1001369.

10.

Cohen

Chen

McCauley

et al . Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011; 365: 493–505.

11.

Ahmad

Howard

Brooks

et al . The role of platelet rich plasma in musculoskeletal science. J R Soc Med Short Rep 2012; 3: 40.

12.

MRCT Center Post-Trial Responsibilities Framework Continued Access to Investigational Medicines. Guidance Document [Version 1.2, November 2017], http://mrctcenter.org/wp-content/uploads/2017/06/2017-06-28-Post-Trial-Responsibilities-Guidance-Document-Version-1.1.pdf (accessed 20 June 2018).

13.

MRCT Center Post-Trial Responsibilities Framework Continued Access to Investigational Medicines. MRCT Center Post-Trial Responsibilities Toolkit [Version 1.1, November 2017]. MRCT Center, http://mrctcenter.org/wp-content/uploads/2017/06/2017-06-26-Post-Trial-Responsibilities-Toolkit-Version-1.0-1.pdf (accessed 20 June 2018).

14.

Kenya National AIDS and STIs Control Programme. Kenya AIDS Indicator Survey 2012: Final Report. Nairobi, NASCOP, www.naccorke/images/documents/KAIS-2012pdf (2014) (accessed 17 November 2017).

15.

Wamoyi

Renju

Moshabela

et al . Understanding the relationship between couple dynamics and engagement with HIV care services: Insights from a qualitative study in Eastern and Southern Africa. Sex Transm Infect 2017; 93(3): e052975.

16.

Kenya Institute for Public Policy Research and Analysis (KIPPRA). Kenya Economic Report 2012, http://kippraorke/indexphp?option=com_docman&task=doc_view&gid=274&Itemid= (2012) (accessed 1 November 2017).

17.

Bogart

Chetty

Giddy

et al . Barriers to care among people living with HIV in South Africa: Contrasts between patient and healthcare provider perspectives. AIDS Care 2013; 25: 843–853.

18.

Rankin

When docs get annoyed at empowered patients, www.psychologytodaycom/blog/owning-pink/201107/when-docs-get-annoyed-empowered-patients (2011) (accessed 15 October 2017).

19.

Higgins

Mathur

Eckel

et al . Importance of relationship context in HIV transmission: Results from a qualitative case-control study in Rakai, Uganda. Am J Public Health 2014; 104: 612–620.

20.

Jiwatram-Negron

El-Bassel

Systematic review of couple-based HIV intervention and prevention studies: Advantages, gaps, and future directions. AIDS Behav 2014; 18: 1864–1887.

21.

El-Bassel

Wechsberg

WM.

Couple-based behavioral HIV interventions: Placing HIV risk-reduction responsibility and agency on the female and male dyad. Couple Fam Psychol: Res Pract 2012; 1: 94–105.

22.

Burton

Darbes

Operario

Couples-focused behavioral interventions for prevention of HIV: Systematic review of the state of evidence. AIDS Behav 2010; 14: 1–10.

23.

Henderson

Churchill

Davis

et al . Clinical trials and medical care: Defining the therapeutic misconception. PLoS Med 2007; 4: e324.

24.

Aellah

Chantler

Geissler

Global health research in an unequal world: Ethics case studies from Africa. LCCN 2016019492, www.ncbinlmnihgov/books/NBK458764/ (2016) ISBN 9781786390042 (accessed 30 September 2017).

25.

Emanuel

Wendler

Killen

et al . What makes clinical research in developing countries ethical? The benchmarks of ethical research. J Infect Dis 2004; 189: 930–937.

26.

The Medicines for Human Use (Clinical Trials) Regulations 2004, www.legislation.gov.uk/uksi/2004/1031 (2004) (accessed 22 October 2017).

27.

Council for International Organizations of Medical Sciences (CIOMS) in collaboration with the World Health Organization (WHO) (CIOMS-WHO). International Ethical Guidelines for Health-related Research Involving Humans, https://cioms.ch/wp-content/uploads/2017/01/WEB-CIOMS-EthicalGuidelines.pdf (2016) (accessed 3 November 2017).

28.

Cho

Danis

Grady

Post-trial responsibilities beyond post-trial access. Lancet 2018; 391: 1478–1479.