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Research Article

Attitudes and perceptions towards novel objective measures of ARV-based vaginal ring use: Results from a global stakeholder survey

• Randy M. Stalter,
• Jenae Tharaldson,
• Derek H. Owen,
• Eunice Okumu,
• Thomas Moench,
• Natasha Mack,
• Elizabeth E. Tolley,
• Kathleen M. MacQueen

x

• Published: July xiv, 2017
• https://doi.org/ten.1371/journal.pone.0180963

Figures

Abstruse

Results of contempo microbicide and pre-exposure prophylaxis clinical trials have shown adherence to be a pregnant challenge with new HIV prevention technologies. Equally the vaginal ring containing dapivirine moves into two open up label follow-on studies (HOPE/MTN-025 and DREAM) and other antiretroviral-based and multi-purpose prevention technology ring products accelerate through the evolution pipeline, there is a need for more accurate and reliable measures of adherence to microbicide band products. We previously conducted a comprehensive landscape analysis to place new technologies that could be practical to adherence measurement of vaginal rings containing antiretrovirals. To explore attitudes and perceptions towards the approaches that we identified, we conducted a survey of stakeholders with experience and expertise in microbicide and HIV prevention clinical trials. From May to July 2015 an electronic survey was distributed via email to 894 stakeholders; a full of 206 eligible individuals responded to at to the lowest degree 1 question and were included in the data assay. Survey respondents were presented with various objective measures and asked near their perceived acceptability to trial participants, feasibility of implementation past study staff, usefulness for measuring adherence and ethical concerns. Methods that require no boosted input from the participant and require no modifications to the existing ring product (i.e., measurement of residual drug or excipient, or a vaginal analyte that enters the ring) were viewed as being more acceptable to trial participants and more than viable to implement in the field. Respondents saw value in using objective measures to provide real-time feedback on adherence. However, approaches that involve unannounced home visits for sample collection or spot checks of ring apply, which could provide significant value to adherence feedback efforts, were met with skepticism. Additional research on the acceptability of these methods to potential trial participants and trial staff is recommended.

Citation: Stalter RM, Tharaldson J, Owen DH, Okumu E, Moench T, Mack N, et al. (2017) Attitudes and perceptions towards novel objective measures of ARV-based vaginal band use: Results from a global stakeholder survey. PLoS Ane 12(7): e0180963. https://doi.org/10.1371/journal.pone.0180963

Editor: Sten H. Vermund, Yale University Yale Schoolhouse of Public Health, Usa

Received: January x, 2017; Accustomed: June 23, 2017; Published: July 14, 2017

Copyright: © 2017 Stalter et al. This is an open access commodity distributed under the terms of the Artistic Eatables Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original writer and source are credited.

Data Availability: All information used for this report are publicly available from the Harvard Dataverse repository (https://dataverse.harvard.edu/dataverse/ARVring; doi:10.7910/DVN/5RN2GW).

Funding: Financial aid was provided by USAID to FHI 360 under the terms of the Adherence Measurement and Optimization of Long-Interim ARV-Based Vaginal Band Agreement, Help-OAA-A-fourteen-00003. The contents are the responsibility of FHI 360 and practise not necessarily reverberate the views of USAID or the U.s. Government. USAID had no role in the study's pattern, data collection or data assay. USAID was involved in discussions about publication of the results and reviewed and approved the manuscript prior to submission for publication. ReProtect, Inc. provided support in the grade of salary for author TRM, just did not have any additional role in the study design, data collection and assay, decision to publish, or grooming of the manuscript. The specific roles of this writer are articulated in the 'author contributions' section.

Competing interests: The authors take declared that no competing interests exist. Author TRM has a commercial affiliation with ReProtect, Inc. Still, the authors have confirmed that this affiliation does not change their adherence to PLOS One policies on sharing data and materials.

Introduction

Results of contempo microbicide and pre-exposure prophylaxis (PrEP) clinical trials have shown participant adherence to be a significant challenge with new HIV prevention technologies [1–4]. Low levels of product utilize of oral and vaginal gel microbicides have largely impeded the ability to measure product efficacy [2, iv]. The use of vaginal rings for sustained commitment of antiretrovirals (ARV) has widely been viewed every bit a way to overcome adherence challenges shown with oral and vaginal gel products [5]. The recent Phase Three trials of the vaginal ring containing the ARV dapivirine, ASPIRE (MTN-020) and The Ring Written report (IPM 027), showed modest HIV prevention overall amidst women using the product [1, half-dozen]. However, low levels of consistent utilize of the band was cited as an issue in the trials, particularly among younger women, and subsequent analyses showed no detectable protection in participants with low adherence [vii].

As the dapivirine band product moves into two open up label follow-on studies (Hope/MTN-025 and DREAM) [eight] and other ARV-based [nine, 10] and multipurpose prevention applied science rings [11, 12] in before stages of the evolution pipeline are progressing to clinical trials, the need for more reliable and objective measures of adherence of microbicide ring products is greater than ever. In the ASPIRE trial and The Ring Report, measurements of residual drug levels in returned rings and detection of drug in plasma were used to objectively measure ring utilize by participants [ane]. While these measures provide useful information about product apply, they besides accept key limitations. For example, both measures are merely applicative to the study arm using the agile ring product and do not allow for real-time adherence feedback to participants due to the need to preserve study blinding, and due to the time required for sample processing and analysis.

Nosotros recently conducted a comprehensive landscape assay to identify and evaluate new biomarkers and biometric approaches to measure adherence to ARV-based vaginal ring products in clinical trials that may overcome limitations with existing approaches [13]. While we identified numerous methods that are currently being explored in PrEP and microbicide trials (e.yard., hair drug analysis, dry claret spot drug detection), we likewise described other concepts that are still in the proof-of-concept stage or in early on clinical studies. How well these newer methods may be received in the field past participants and study staff needs to be ameliorate understood before they are developed further and implemented in clinical trials. To explore attitudes and perceptions towards a number of the approaches that we identified, nosotros conducted a survey of stakeholders with feel and expertise in microbicide and HIV prevention clinical trials. Our intent in surveying this population was to understand how stakeholders perceived and interpreted written report participant perspectives and beliefs, and the extent to which they would notice diverse options for measuring and supporting adherence in clinical trials to be acceptable, viable, useful and ethical when implemented in the field.

Methods

Study participants

From May to July 2015 an electronic survey was distributed via email to 894 stakeholders with feel and expertise in HIV prevention clinical trial pattern and implementation. The purpose of the survey was to assess stakeholders' attitudes and perceptions toward various methods of adherence support and measurement in clinical trials involving ARV-based vaginal rings, including objective measures of adherence. Stakeholder contact information was gathered from publicly accessible websites and databases. Members of the major HIV prevention research networks (i.eastward., Microbicide Trials Network and HIV Prevention Trials Network), the Consortium for Band Adherence and attendees of the 2014 HIV Research for Prevention (HIV R4P) meeting were specifically targeted.

The survey instrument was developed in Qualtrics. We established face up validity with the tool by having the survey questions reviewed independently by internal and external colleagues with survey construction and content expertise. Nosotros conducted a limited pilot exam with in-business firm colleagues who met eligibility requirements for the survey. The survey was sent out to the start grouping of stakeholders on May 18, 2015 via email. The email independent a short description of the purpose of the study followed past an electronic link to the survey itself. Two boosted waves of recruitment emails were sent on June 1 and June 11, 2015. The survey remained open until July 6, 2015.

Inclusion criteria included being 18 years of age or older, having written English fluency, and having active involvement in the previous 24 months in at to the lowest degree i of the following roles or activities related to an ARV-based HIV prevention trial, or coincident research directly related to such a trial, that enrolled women equally participants: protocol team member; trial implementation staff (eastward.1000., investigator, manager, coordinator); program officer from funding system; adherence and production employ counselor; trial participant recruiter; trial monitor; community liaison officer, outreach worker or educators; ethics review committee member or administrators; or ethics consultant. Of the 894 emails sent to stakeholders, 115 (13%) bounced dorsum resulting in 780 emails that reached the intended private. A total of 258 (29%) opened the link to the online survey and completed the eligibility questions and 225 (25%) met the eligibility requirements. Of those who were eligible, 219 (97%) consented to participate and 206 (92%) responded to at least 1 survey question and were included in the data assay; 152 (68%) respondents completed the entire survey.

Measures

Survey respondents were asked to give basic sociodemographic information including their gender, age, highest degree or level of education, geographic location and previous office(southward) in HIV prevention clinical trials. Questions relating to biomarkers and biometric measures of adherence were based on findings from our previous landscape analysis. We asked stakeholders almost several existing and hypothetical objective adherence measures including:

• use of a magnetometer to detect a magnet integrated into the vaginal band for spot checks during unannounced home visits
• measurement of systemic assimilation of a volatile taggant incorporated into the ring formulation using a breath exam
• collection of hair, claret and vaginal fluid samples at random, unannounced dwelling house visits for analysis of drug content
• the use of an integrated electronic sensor or logger in the ring that could record continuous data on intravaginal temperature, pH, pressure level or exposure to the external environment if the ring is removed
• measurement of rest drug levels in the ring in one case it is returned
• measurement of residue levels of a non-drug excipient that is either intrinsic to the band's formulation or added to the ring
• measurement of aggregating of a known vaginal analyte in the ring one time it is returned

Subsequently receiving a brief clarification of each of the adherence measures mentioned above, the stakeholders were asked to reply questions almost their perceived acceptability to trial participants, feasibility of implementation by study staff, usefulness for measuring adherence, and ethics effectually use with trial participants. For some questions, stakeholders were asked to evaluate methods using a Likert calibration-blazon format. In other instances, they were asked to rank the measures based on each of the criteria mentioned above or choose a certain number of methods that they felt most and least met the criteria. For some methods, follow-up questions were included about specific aspects of the technologies. Stakeholders were also asked well-nigh their views on providing participants feedback on their adherence and the likelihood of participants tricking or outsmarting the adherence measures during a trial.

Information collection and analysis

Survey responses were compiled in Qualtrics. Later on information collection was completed, quantitative data were transferred to SPSS 17.0 for data cleaning and analysis. Categories for several variables, including age, geographic location and highest degree or level of didactics, were merged when cell counts were small and/or when categories were conceptually compatible. Three main categories of clinical trial roles were constructed based on the responses received: administrative/supervisory, field staff, and programme officeholder/ethical reviewer. Administrative/supervisory roles include protocol team members and trial implementation staff (e.grand., investigator, manager, coordinator); field staff include adherence and production utilize counselors, trial participant recruiters, and community liaison officers, outreach workers or educators; program officeholder/upstanding reviewer roles include program officers at funding organizations, trial monitors, ethics review committee members/administrators and ethics consultants.

Chi-square tests were used to assess associations between categorical variables, where advisable. In cases where expected frequencies were less than 5 for some crosstabulation cells, Fisher's exact tests were used. All tests were assessed at the 5% significance level for two-sided comparisons.

Qualitative analysis was carried out on questions that allowed for open-concluded responses. For each question with qualitative responses, i of three coders reviewed the responses and identified recurring and potentially meaning themes. The three coders convened and discussed common themes and summarized findings from each question in a memo.

Ethics

This study protocol was submitted to FHI 360's Protection of Homo Subjects Committee and was deemed exempt every bit it was determined that the study posed minimal risk to survey respondents. Potential survey respondents were informed via email about the purpose of the research, methods of stakeholder identification, that participation was voluntary, how confidentiality was going to exist maintained, that risks were minimal and that in that location were no direct personal benefits for participating and who to contact for information on the research and their rights as report participants. Upon accessing the survey, the stakeholders were presented with a consent statement and eligibility screener. If interested and found to be eligible, they were given the option to have or decline consent to be included in the study. Those who accepted consent were immune to embark the survey.

Results

Respondent characteristics

Of the 894 emails sent to stakeholders, 115 (13%) bounced back resulting in 780 emails that reached the intended individual. A total of 258 (29%) stakeholders opened the link to the online survey and completed the eligibility questions and 225 (25%) met the eligibility requirements. Of the stakeholders who were eligible, 219 (97%) consented to participate and 206 (92%) responded to at least one survey question and were therefore included in the data analysis; 152 (68%) respondents completed the survey.

Well-nigh survey respondents (64.1%) were xl years of age or older, 35% were between 25–39 years erstwhile and one respondent was between 18–24 years old (Table 1). Of the respondents who provided their gender, 74.3% were female and 25.7% male. Most respondents who provided their highest level of education reported having a master's or doctoral degree (64.5%) and approximately a quarter had an undergraduate degree. Of the respondents who reported their geographic location, simply over one-half were from Sub-Saharan Africa, 39% from North America, and the remaining 10% from South or Fundamental America, the Caribbean, South or Southeast Asia, Europe or Australia. Nearly three-quarters of participants stated that they had an administrative or supervisory office in HIV prevention trials within the past 24 months, 35.4% reported having held a position in the field, and 14.vi% were program officers for a funding organization or upstanding reviewer.

Trial participant acceptability

Nosotros first asked HIV prevention trial stakeholders about their views on the potential acceptability of diverse biometric measures of ring adherence to clinical trial participants. Equally shown in Fig 1, of the methods presented, analysis of returned rings for residual drug levels, measurement of depletion of an inactive ingredient out of the ring or measurement of a vaginal analyte that enters the ring during use were thought to be most acceptable to trial participants. Although these methods measure out adherence differently, they were combined as one option for questions on acceptability as they would crave the same level of input from the trial participant, which is only to turn the band over at their designated follow-upwards visit for analysis. Nearly 90% of respondents believed these approaches would be very acceptable or somewhat acceptable to women.

The utilise of a jiff exam to discover chemical taggants added to the band conception and the drove of pilus samples for drug levels were too viewed as potentially being acceptable to women. Given past studies that showed the chemical taggants used for the jiff test approach in vaginal gel products caused an unfavorable gustatory modality for some women [14, fifteen], survey respondents were asked an boosted question about women's credence of the method if they knew information technology would result in an unfavorable gustation. Over 3-quarters (78.half dozen%) of respondents said that it was very likely or somewhat likely that women would refuse the method if this was the case (information not shown).

For the method of collecting and analyzing pilus samples, we asked a follow-up question about whether respondents knew of any cultural barriers toward removal of 20–thirty strands of hair for analysis, which is roughly the amount of pilus needed to detect most ARVs in assays. Most of those who responded cited cultural beliefs equally a factor that may prevent acceptance of hair removal. Witchcraft was often mentioned (59.four% of respondents) as a reason for why some women would oppose this method. In particular, many respondents mentioned Africans, Black Africans, and African cultures in general beingness opposed to this approach, and two respondents specifically reported people from the Zulu culture being opposed. Of those respondents who mentioned witchcraft as a bulwark to uptake, several said that some people might be concerned with the disposal of hair once it is cut or removed from i's head and that information technology would need to be disposed of properly (e.g., buried) to avoid the person becoming bugged. Some respondents also cited women's pilus styles and hairdos, and their desire to protect them, as a factor that would brand some women be opposed to giving hair samples. Similarly, it was reported that people with curt pilus might dislike this exercise as blank spots may go noticeable over time.

The arroyo that was perceived to be least acceptable to women was the detection of a magnet integrated into the ring using a handheld magnetometer. Only 63.9% of respondents said that the method would either be very acceptable or somewhat acceptable to participants. Just over half (54.8%) of respondents believed this method would be very or somewhat acceptable if done in conjunction with unannounced dwelling house visits. In a follow-up question, 35.7% said that women would be very skeptical or worried and 53.2% would be somewhat skeptical or worried to have a magnet inside their bodies.

Farther analysis showed that views on acceptability for hair sampling differed by respondent role and geographic location but not for other methods (information not shown). Those who had an administrative or supervisory part in HIV prevention trials in the by 24 months were more likely than those who did not to believe hair sampling would be very or somewhat acceptable to trial participants (86.6% vs. 63.0%; p = 0.009). Additionally, respondents from the Americas, Europe or Australia were marginally more probable to view hair sampling as being very or somewhat adequate to trial participants than respondents from Sub-Saharan Africa (89.viii% vs. 76.half dozen%; p = 0.051); responses did not significantly differ between respondents in South or Southeast Asia and other areas of the world. Views on acceptability were non associated with respondent age, gender or teaching level for whatsoever adherence measure.

Feasibility of implementation

Stakeholders were also asked to give their opinion on how feasible implementation of various biometric measures would be in clinical trials. Like the findings on acceptability, analysis of returned rings for residual drug, a not-active excipient that diffuses out of the ring, or an analyte that enters the ring were viewed as being nearly viable, with 91.4%, 88.6% and 85.1% of respondents indicating that these approaches would be very or somewhat viable, respectively (Fig 2). Collection of hair samples was too seen as existence quite feasible, with nearly 85% of respondents indicating that this arroyo would be very or somewhat feasible. Collection of blood samples, collection of vaginal fluid through self-swabbing and detection of rings using an integrated magnet at unannounced visits were viewed equally being the least viable. Of those who responded, 28.1%, 22.3% and 17.1% reported these methods would non exist viable, respectively.

Our analyses showed that views on the feasibility of pilus collection as a measure of adherence was associated with respondent role and location. Respondents who held authoritative or supervisory roles in HIV prevention trials were more than likely to view hair drove as being very or somewhat feasible to implement in the field than those who did not (93.8% vs 77.viii%; p = 0.02). Additionally, respondents who held a field-level position were less likely to view pilus drove as very or somewhat viable than those who had non (94.9% vs. fourscore.5%; p = 0.02). Respondents in America, Europe and Australia were more probable to view hair collection every bit beingness very or somewhat feasible than respondents in Sub-Saharan Africa (98.iii% vs. 84.six%; p = 0.007). Respondents with more education (i.due east., master's or doctoral caste) were more likely to view blood drove as being very or somewhat feasible when compared to respondents with less education (i.e., undergraduate caste or less) (79.six% vs. 59.1%; p = 0.012). Views on feasibility were non associated with respondent age or gender for any adherence measure.

Method usefulness

Stakeholders were asked to identify which of the biomarkers and biometric approaches presented to them would be most useful for measuring vaginal ring adherence. As shown in Fig iii, measurement of residual drug in returned rings was viewed as existence the most useful approach, with 67.2% of all respondents identifying information technology as one of the near useful approaches. The use of a ring with an integrated electronic sensor to make biometric measurements (e.g., temperature, pH, pressure level monitoring) was also viewed as a highly useful approach. Those approaches that involved unannounced dwelling visits were seen as beingness the least useful. Only 30.five%, 31.3%, 34.iv% and 39.1% of respondents identified blood collection, jiff tests, vaginal fluid collection and spot checks using a band with an integrated magnet at unannounced abode visits as 1 of the well-nigh useful measures of adherence, respectively.

Upstanding considerations

Survey respondents were asked to specify whether they believed each of the methods to be ethical, potentially ethical or definitely unethical to use in a clinical trial setting. The frequencies of respondents who showed some business concern about the ideals of specific methods (i.e., either responded that the approach was potentially or definitely unethical) are shown in Fig 4. Respondents showed the least concern for measurement of residual drug, a non-active excipient that diffuses out of the ring, or a vaginal analyte that enters the ring. Many respondents indicated ethical concerns for the methods that involved unannounced home visits. The method viewed as least upstanding was conducting spot checks of rings with an integrated magnet using unannounced home visits, with 67.9% indicating that the method was potentially unethical or definitely unethical.

Respondents' views on the ethics of hair collection were shown to be associated with their geographic region and clinical trial role (data not shown). Respondents in Sub-Saharan Africa were more than likely to think hair collection was potentially or definitely unethical when compared with respondents in the Americas, Europe or Australia (41.4% vs. eight.5%; p<0.001). Individuals with field-based positions were more probable to view pilus drove as potentially or definitely unethical than those who did not accept field-based roles (43.two% vs. 22.i%; p = 0.02) whereas individuals with an administrative/supervisory office were more likely to see hair sample drove as being an upstanding approach (78.5% vs. 38.1%; p<0.001) when compared to those who had non held an authoritative/supervisory role. Individuals with an authoritative/supervisory function were also more probable to view measurements of analyte aggregating into the ring as upstanding (91.0% vs. 70.0%; p = 0.021). Finally, younger respondents (i.eastward., eighteen–39 years of age) were more than likely say that detection of a magnetic ring during unannounced domicile visits would be potentially or definitely unethical than older respondents (i.e., 40+ years of age) (86.4% vs. 69.ii%; p = 0.035). Views on ethics were non associated with respondent gender or educational activity for any adherence measure out.

Trial participant adherence feedback

Some of the biometric measures identified in our previous landscape analysis allow for real-time feedback on adherence, including the use of rings with integrated magnets or RFID tags to conduct spot checks or examining the color of worn rings. When asked whether participants should exist given feedback well-nigh their adherence during a trial based on biomarker or biometric results, responses were positive with 84.vii% of respondents agreeing with this statement. When stakeholders were asked about what they idea to exist an appropriate frequency to provide adherence feedback to trial participants, 50.3% of those surveyed said at every follow-upwardly visit (the typical schedule of follow-up visits has been monthly in the context of biomedical HIV prevention trials, including those of vaginal rings) and 38.5% said 2–4 times per yr. Simply six.3% said that counselors should not give participants feedback on adherence based on objective measures. Additionally, of all survey respondents, 95.8% indicated that trial staff would detect providing feedback to women very adequate or somewhat acceptable and 95.1% indicated that trial participants would find receiving feedback very acceptable or somewhat acceptable (information not shown).

Method manipulation

Finally, respondents were asked whether the proposed measures would be susceptible to being tricked or outsmarted by trial participants. Generally, those who responded were hundred-to-one that trial participants would effort to play a trick on or outsmart adherence measures. Only 8% said many or virtually participants would try to outsmart these measures while 46% said that some but non most participants would effort it (information not shown). However, stakeholders identified certain biometric measures as being more susceptible to manipulation than others should participants try to do and then. Rings with integrated electronic sensors and collection of vaginal fluid via cocky-swabs were thought to be most susceptible to being outsmarted (Fig v). Pilus sample drug analysis, measurement of blood drug levels and residual drug measurements were seen every bit the three methods that were least probable to exist outsmarted. Farther analysis showed that views on participant'due south likelihood to manipulate adherence measures did not vary by respondent historic period, gender, instruction, location or part (data not shown).

Discussion

A better understanding of women's adherence to ARV-based vaginal rings is critical for assessing product effectiveness in future clinical trials. We previously conducted a mural analysis to identify new and existing technologies that can be practical toward measurement of vaginal ring adherence [13]. With this survey, we aimed to obtain valuable formative information nearly HIV prevention stakeholders' views on the implementation of many of the measures identified in this landscape analysis.

Measures that were viewed past stakeholders to exist most acceptable to participants and feasible for clinical trial staff to implement were measurements of residual drug in the ring, a vaginal analyte that enters the band during apply and depletion of a non-drug excipient out of the ring. This finding is not surprising considering that these approaches are non-intrusive and crave no additional input from participants than existing procedures. Sample collection simply involves retrieving the ring from the participant at designated follow-upwards visits. These methods may too be viewed more favorably considering no alterations to the existing ring product are required. Women may take consequence with use of rings that include electronics, magnets or other unknown entity. Furthermore, from a clinical trial management perspective, modifying the ring may lead to additional costs and regulatory and ethical issues.

Stakeholders believed the measurement of residuum drug to be the most useful followed past apply of an electronic sensor in the band and the measurement of depletion of a not-drug excipient from the band. Measurement of residuum drug has been explored in the clinical trials of the dapivirine band, with analyses showing a decrease in drug concentration afterward longer periods of utilize [16]. A major disadvantage of this method, nonetheless, is that it can merely exist used with the arm of the trial using the active ring product. Therefore, as long as a placebo band is required for apply with a comparing group, this method will exclude a portion of the study sample, and raises the potential for bias in the event that adherence behaviors correlate with risk taking behaviors. Considering of this, we recommend exploring methods to mensurate the diffusion of a vaginal analyte into the ring, and methods to measure depletion of a not-drug excipient out of the ring, as these approaches can be applied to both active and placebo band products [xiii, 17, eighteen].

Drove of hair samples was also viewed by stakeholders as being adequate to participants, feasible to implement, useful to mensurate adherence and being at the lowest risk for participants manipulating the method. We have previously identified this method as being of high priority for further evolution due to the ease of sample collection, transport and storage and strong correlations shown between hair drug levels and oral doses of tenofovir [nineteen] and other adherence measures [twenty, 21]. Additionally, novel assays aimed at lowering the price of pilus sample assay [22] and providing college resolution quantification of drug levels [23] are in development.

While these findings from the stakeholders are promising, it is important to admit that acceptability of hair collection will likely vary between different populations and settings. Stakeholders from Sub-Saharan Africa in our survey seemed to perceive this approach as being less acceptable to trial participants than stakeholders in the Americas, Europe and Commonwealth of australia. Other studies in Kenya and Uganda have reported ≥95% participant acceptability of the method [xx, 24], while qualitative information from South Africa shows participants may exist reluctant to donate hair due to fear of the hair existence used in witchcraft or other means to inflict impairment [25]. A written report involving pilus collection from children in rural Uganda proved to be challenging due to participants declining sample collection or already having their heads clean-shaven [26]. Therefore, it is important that further research on the acceptability of pilus collection be done, peculiarly in populations where trials will be conducted, and community sensitization and pedagogy take place to dispel myths (e.g., its potential use for witchcraft) and maximize uptake during a trial.

Our results suggest that the stakeholders see value in providing participants with existent-fourth dimension feedback on adherence using biometric measures and that participants and trial staff may be welcoming to this approach. Unfortunately, the methods that are the nearly useful for facilitating the provision of real-time feedback, i.east., the approaches that involve unannounced home visits for sample collection or spot checks of band use, were met with overwhelming skepticism. Not only were approaches involving unannounced dwelling visits seen as existence problematic from acceptability, feasibility and ethical standpoints, simply very few stakeholders saw them as beingness useful adherence measures. Follow-upward questions were non asked about the specific problems stakeholders had with these approaches, but nosotros speculate that their concerns with unannounced visits prevarication with the potential invasion of privacy, inadvertent 'outing' of women as HIV prevention trial participants and/or, in the instance of the use of an integrated magnet, concerns about the safety of the device. Bear witness from recent HIV prevention trials has shown women may avoid disclosing study participation to their partner or members of their community out of fear of negative reactions (e.g., partner disapproval or discrimination by peers), questioning or misattribution of participation to having an HIV-positive condition [27–31]. Provision of educational materials such as information leaflets or opportunities for direct contact with investigators have been suggested as ways to amend partner and community understanding about the study and product [28], which may help to assuage participant concerns almost 'outing' from adherence measures. Motivational support for product adherence combined with targeted support for identifying and implementing behaviors that facilitate adherence also bear witness show of effectiveness [32]. Counseling nigh the safety and risks of whatever new or strange technology used in the ring to monitor employ will also be critical to maximize production uptake and adherence.

Despite these findings, nosotros all the same believe it would be a worthwhile effort to collect additional data on the acceptability of unannounced visits as this approach would add tremendous value to adherence back up efforts. Previous research has shown that unannounced pill counts, while resource intensive, tin be an effective arroyo to monitoring adherence in clinical studies [33–35]. Until more than inquiry is washed, information technology would be premature to conclude that this would be infeasible when used with other adherence measures.

Nosotros acknowledge some potential limitations with this written report. First, the use of an online survey is susceptible to selection bias as it is limited to those with cyberspace access during the timeframe the survey was open and those whose contact data was available in the databases searched. As only 206 (23%) of the 894 individuals who were invited to participate in the survey were included in data analyses and approximately nine in ten respondents were from Northward America or Sub-Saharan Africa, results may not be representative of the entire HIV prevention trial field. Additionally, stakeholders' views on acceptability may not reflect the attitudes and perceptions of actual trial participants. Therefore, additional acceptability research involving past or potential trial participants is needed. Likewise, while nosotros did provide descriptions of the biometric methods presented in the survey, we were non able to clarify details or answer questions respondents may have had. Therefore, questions may have been answered with incomplete or inaccurate understanding about the specific technologies.

Our results show that vaginal ring adherence measures that require no additional input from the participant and require no modifications to the existing ring production (due east.g., measurement of residual drug or excipient, or a vaginal analyte that enters the ring) are viewed by HIV prevention trial stakeholders to be most likely to be accepted by trial participants and volition be nigh feasible to implement in the field. Collection of hair samples was also seen to bring value to trials involving ARV-based rings but views differ by respondents' geographic location and role in clinical trials. Methods that involve unannounced dwelling visits are seen as being well-nigh problematic and heighten ethical concerns. However, given their value in providing existent-time adherence feedback to participants, additional research on methods that involve unannounced visits may all the same be worthwhile. We recommend farther investigation of these approaches to make full the gaps in existing adherence measures and allow for more than authentic appraisals of vaginal ring use.

Supporting information

Acknowledgments

We would similar to give thanks all of the HIV prevention stakeholders who participated in the survey for generously giving their time and input. Cheers also to Dr. Mario Chen for his guidance on the statistical analyses carried out for this study.

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