HIV Prevention Clinical Trials Research Articles

The pathway to delivering injectable CAB for HIV prevention: strategies from global PrEP leaders leveraging an adapted version of the Intervention Scalability Assessment Tool (ISAT)

BackgroundLonger-acting cabotegravir (CAB) is a novel, safe, and efficacious pre-exposure prophylaxis (PrEP) for HIV prevention. As we near a time for CAB scale-up, the experience of global leaders in PrEP research and implementation can be leveraged to identify optimal strategies for scaling and integrating CAB into existing PrEP infrastructure worldwide.MethodsWe recruited leaders of HIV prevention clinical trials and large PrEP programs through a combination of purposive and snowball sampling for participation in individual interviews. We conducted interviews using a semi-structured guide that compared CAB to oral PrEP and sought perspectives on barriers and strategies for CAB scale-up. Interviews were conducted virtually, audio recorded, and transcribed. We used thematic analysis, grounded in an adapted version of the Intervention Scalability Assessment Tool (ISAT), to identify critical elements for optimizing delivery of CAB.ResultsFrom October 2021 to April 2022, we interviewed 30 participants with extensive experience in PrEP research, care, and programming. Participants worked in all seven WHO regions and reported a median of 20 years working in HIV and 10 years in PrEP. Participants agreed that CAB was efficacious and discrete, therefore having the potential to address current concerns about oral PrEP adherence and stigma. Participants indicated direct and indirect costs for provider training, expansion of existing medical infrastructure, and the current medication cost of CAB as major concerns for roll out. The true cost to the end-user and health system were unknown. There were some conflicting strategies on how to best address product targeting, presentation of efficacy, and timing of product availability with scale-up. Some thought that targeting CAB for the general population could normalize PrEP and decrease stigma, while others thought that prioritizing key populations could optimize impact by targeting those with highest risk. Overall, participants emphasized that to ensure successful CAB scale-up, communities and stakeholders must be involved at every stage of planning and implementation.ConclusionsOur evaluation found that although there is a clear and urgent need for additional HIV PrEP options beyond daily oral PrEP, CAB scale-up must be thoughtful, flexible, and based in lessons learned from oral PrEP rollout.

The Prevalence and Correlates of Sexually Transmitted Infections (STIs) among Heterosexual HIV-1 Sero-Discordant Couples Enrolled into HIV Prevention Clinical Trial in Western Kenya

The Prevalence and Correlates of Sexually Transmitted Infections (STIs) among Heterosexual HIV-1 Sero-Discordant Couples Enrolled into HIV Prevention Clinical Trial in Western Kenya

Spatial variations in STIs among women enrolled in HIV prevention clinical trials in Durban, KwaZulu-Natal, South Africa

ABSTRACT South Africa is faced with a high HIV and STI prevalence and incidence, respectively, with pockets of high burden areas driving these diseases. Localised monitoring of the HIV epidemic and STI endemic would enable more effective targeted prevention strategies. We assessed spatial variations in curable STI incidence among a cohort of women enrolled in HIV prevention clinical trials between 2002 and 2012. STI incidence rates from 7557 South African women enrolled in five HIV prevention trials were geo-mapped using participant household GPS coordinates. Age and period standardised incidence rates were calculated for 43 recruitment areas and Bayesian conditional autoregressive areal spatial regression (CAR) was used to identify significant patterns and spatial patterns of STI infections in recruitment communities. Overall age and period standardised STI incidence rate were estimated as 15 per 100 PY and ranged from 6 to 24 per 100 PY. We identified five significant STI high risk areas with higher-than-expected incidence of STIs located centrally (three-locations) and southern neighbouring areas of Durban (two-locations). Younger age (<25), not married/cohabitating, parity <3 and poor education were all significant correlates of high STI communities. Findings demonstrate sustained STI incidence rates across the greater Durban area. The role of STI incidence in HIV acquisition in high HIV endemic areas need to be revisited as current highly effective PrEP interventions do not protect from STI acquisition. In these settings there is an urgent need for integrative HIV and STI prevention and treatment services.

Parental Engagement in Consent Processes for Enrollment in Biomedical HIV Prevention Trials: Implications for Minor Adolescents' Willingness to Participate

PurposeMinor adolescents are often excluded from HIV prevention clinical trials due to unresolved ethical issues. Their under-representation in research leads to delayed access to new HIV prevention approaches. We examine the relationship between consent procedures, trial features, demographic and social characteristics, and minor adolescents' willingness to participate (WTP) in biomedical HIV prevention research. MethodsWe recruited 14–17-year-olds at risk of HIV for this quasi-experimental study. Adolescents were randomly assigned to (1) self-consent, (2) adult permission required, or (3) parental permission required and underwent simulated consent procedures for two types of HIV prevention trials. They rated likelihood of participating in each study if offered the opportunity and completed a survey with demographic, social, and behavioral measures. ResultsOne hundred and twenty nine adolescents with diverse identities and socioeconomic status enrolled. Among the 58% of participants who identified as lesbian, gay, bisexual, transgender, or queer (LGBTQ), 76% were out to at least one parent/guardian (outness). Mean WTP was 3.6 (of 5; 5 = definitely would participate) across all participants and both trial types. We found no evidence of an association between WTP and consent condition, LGBTQ identity, or outness. However, medical mistrust, communication with parents, and concern about HIV were associated with WTP. DiscussionOur results suggest adolescents are willing to participate in HIV prevention trials and parental involvement in the consent process may not be the most important deciding factor. However, variation in WTP within consent groups, and variation in other significant variables, underscores the need for individualized approaches to recruitment and consent for these trials.

Twenty years of Prevention of Mother to Child HIV Transmission: research to implementation at a national referral hospital in Uganda.

Over 90% of new paediatric HIV infections are acquired through mother to child transmission. Prevention of mother to child HIV transmission (PMTCT) research in sub-Saharan Africa informed WHO guidelines which enabled implementation of PMTCT programs globally. To describe Makerere University-Johns Hopkins University (MU-JHU) perinatal HIV prevention research and implementation of the Mulago National Referral Hospital (MNRH) PMTCT program. Perinatal HIV prevention studies conducted at MU-JHU between 1997-2016 were summarized. Program aggregated data was extracted and analyzed using STATA 15. In 1999, the HIVNET 012 study demonstrated that single-dose nevirapine (sdNVP) to the mother at onset of labor and to her newborn, reduced MTCT by nearly 50%. In 2016, the PROMISE study documented the safety and efficacy of ART during pregnancy and breastfeeding period. Program implementation at MNRH started in 2000. Uptake of HIV testing increased from 70% to 99% from 2006 onwards. sd NVP was the initial ARV regimen but by 2012, MOH recommended Option B+(triple therapy). MTCT rates reduced from 16.9% in 2001 to 2.3% in 2020. Perinatal HIV prevention clinical trials conducted at MU-JHU provided evidence to inform WHO PMTCT guidelines. MNRH program evaluation demonstrated the significant decline in MTCT rates over the last two decades.

A Layer Plus Approach to Implementation Research and Collaboration for Long-Acting Injectable Preexposure Prophylaxis for HIV Prevention.

In 2020, the HIV prevention clinical trials, HPTN (HIV Prevention Trials Network) 083 and 084, reported that long-acting injectable cabotegravir (CAB-LA) for HIV prevention was statistically superior to daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for pre-exposure prophylaxis (PrEP) in cisgender men and transgender women who have sex with men, and cisgender women. However, clinical efficacy does not translate to real-world effectiveness and clinical practice as evidenced by current global use of oral PrEP. There are ~626,000 users of PrEP, which is significantly below the 3 million goal set by UNAIDS for 2020. Implementation will be key to ensuring that CAB-LA reaches those who desire to use it. We describe the Layer Plus Approach for CAB-LA for PrEP dissemination and implementation. The "Layer" is focused on integrating CAB-LA into existing PrEP models of care and understanding the best delivery channels that could be established in existing programs. Important implications of layering include preparing health professionals to provide CAB-LA, improving access for potential users, and addressing existing PrEP structural and facility barriers. "Plus," which accounts for the existing disparities in PrEP access and use, means expanding CAB-LA to reach individuals for whom HIV prevention options have not been accessible or who have lapsed on oral PrEP. Implications for Plus include the development of new structures, systems, policies, and processes. A key aspect to the Approach is building collaborations to aid successful implementation. The Layer Plus Approach is a simple but strategic framework or a tailored approach to guide dissemination research and implementation.

Stakeholders engagement and advocates' role in biomedical HIV prevention clinical trials – Perspectives of advocates working in Africa

Stakeholders engagement and advocates' role in biomedical HIV prevention clinical trials – Perspectives of advocates working in Africa

Strategies implemented for accurate dispensing of an investigational new drug in a multi-site HIV prevention clinical trial

Safe practices for dispensing investigational product (IP) during clinical trials are not standardized and information in this regard is often limited. ASPIRE was a Phase 3 safety and effectiveness trial of a vaginal matrix ring containing 25 mg of dapivirine for the prevention of HIV-1 in women. The study enrolled 2629 women at 15 clinical research sites in Malawi, Uganda, South Africa and Zimbabwe who were randomized in a 1:1 ratio to receive either a vaginal ring containing 25 mg of dapivirine or a matching placebo vaginal ring. The vaginal rings and packaging were identical in appearance in order to maintain the study blind. A real-time, documented second check of the dispensing process was conducted by a second pharmacy staff. Frequent inventory counts and real time accountability audits were also useful for rapidly identifying a dispensing error. A total of 52,625 vaginal rings were dispensed with only three documented pharmacy dispensing errors. There were zero dispensing errors at 13 of the 15 sites with an overall rate of <1.0 per 10,000 rings dispensed. Our study findings support the implementation of a double check dispensing process and real time accountability audits as standard practice in clinical trials.

Adaptation and validation of simple tools to screen and monitor for oral PrEP adherence.

Oral, vaginal and other pre-exposure prophylaxis (PrEP) products for HIV prevention are in various stages of development. Low adherence poses a serious challenge to successful evaluation in trials. In a previous study, we developed tools to screen for general adherence and specifically monitor intravaginal ring adherence within the context of HIV prevention clinical trials. This study aimed to further validate the screening tool and to adapt and provide initial psychometric validation for an oral pill monitoring tool. We administered a cross-sectional survey between June and October 2018 at a trial site located near Cape Town, South Africa, and another in Thika, Kenya, with 193 women who had experience using daily oral pills. We fit confirmatory factor analysis models on the screening tool items to assess our previously-hypothesized subscale structure. We conducted an exploratory factor analysis of oral PrEP monitoring items to determine the underlying subscale structure. We then assessed the construct validity of each tool by comparing subscales against each other within the current sample and against our original sample, from a study conducted in four sites in South Africa, including Cape Town. The screening tool structure showed moderate evidence of construct validity. As a whole, the tool performed in a similar way to the original sample. The monitoring tool items, which were revised to assess perceptions about and experiences using daily oral PrEP, factored into five subscales that showed moderate to good reliability. Four of the five subscales had a similar structure overall to the vaginal ring monitoring tool from which they were adapted. Accurate measurement of HIV-prevention product adherence is of critical importance to the assessment of product efficacy and safety in clinical trials, and the support of safe and effective product use in non-trial settings. In this study, we provide further validation for these measures, demonstrating the screening tool's utility in additional populations and adapting the monitoring tool's utility for different HIV-prevention products.

HIV and Aging Comes into the Spotlight: 2013 to Now

I have had the pleasure of serving as Co-Convener of the HIV, AIDS and Older Adults Special Interest Group (SIG) for seven years (2013 to now). During this time, we witnessed an increase in NIH funding opportunities, most notable was the Multidisciplinary Studies in HIV/AIDS and Aging FOA. NIH also renewed its support for two prominent longitudinal HIV cohort studies (now knowns as the Combined Cohort Study) because of their unmatched ability to provide insight on the effects of HIV infection and aging. Individuals older than 50 years of age are now included in AIDS and HIV prevention clinical trials. And, in 2008 the AIDS Institute launched the first National HIV/AIDS and Aging Awareness Day (Sept 18th). During this period, the SIG continued to raise awareness about HIV and aging through sponsored symposia and Webinars, and participants for the SIG participated in the first HIV and aging GSA Momentum Discussion. Part of a symposium sponsored by the HIV, AIDS and Older Adults Interest Group.

Addressing Ethical Challenges in US-Based HIV Phylogenetic Research.

In recent years, phylogenetic analysis of HIV sequence data has been used in research studies to investigate transmission patterns between individuals and groups, including analysis of data from HIV prevention clinical trials, in molecular epidemiology, and in public health surveillance programs. Phylogenetic analysis can provide valuable information to inform HIV prevention efforts, but it also has risks, including stigma and marginalization of groups, or potential identification of HIV transmission between individuals. In response to these concerns, an interdisciplinary working group was assembled to address ethical challenges in US-based HIV phylogenetic research. The working group developed recommendations regarding (1) study design; (2) data security, access, and sharing; (3) legal issues; (4) community engagement; and (5) communication and dissemination. The working group also identified areas for future research and scholarship to promote ethical conduct of HIV phylogenetic research.

Views among Malawian women about joining HIV prevention clinical trials when pregnant

BackgroundThe pressing need to expand the biomedical HIV prevention evidence base during pregnancy is now increasingly recognized. Women’s views regarding participation in such trials and initiating PrEP while pregnant are critical to inform evolving policy and best practices aimed at responsibly expanding evidence-based access for this population.MethodsWe conducted 35 semi-structured interviews with reproductive-aged women in Malawi in the local language, Chichewa. Participants were HIV-negative and purposively sampled to capture a range of experience with research during pregnancy. Women’s perspectives on enrolling in three hypothetical HIV prevention trial vignettes while pregnant were explored, testing: (1) oral PrEP (Truvada) (2) a vaginal ring (dapivirine), and (3) a randomized trial comparing the two. The vignettes were read aloud to participants and a simple visual was provided. Interviews were audio-recorded, transcribed, translated, and coded using NVivo 11. Thematic analysis informed the analytic approach.ResultsA majority of women accepted participation in all trials. Women’s views on research participation varied largely based on their assessment of whether participation or nonparticipation would best protect their own health and that of their offspring. Women interested in participating described power dynamics with their partner as fueling their HIV exposure concerns and highlighted health benefits of participation—principally, HIV protection and access to testing/treatment and ancillary care, and perceived potential risks of the vignettes as low. Women who were uninterested in participating highlighted potential maternal and fetal health risks of the trial, challenges of justifying prevention use to their partner, and raised some modality-specific concerns. Women also described ways their social networks, sense of altruism and adherence requirements would influence participation decisions.ConclusionsThe majority of participants conveyed strong interest in participating in biomedical HIV prevention research during pregnancy, largely motivated by a desire to protect themselves and their offspring. Our results are consistent with other studies that found high acceptance of HIV prevention products during pregnancy, and support the current direction of HIV research policies and practices that are increasingly aimed at protecting the health of pregnant women and their offspring through responsible research, rather than defaulting to their exclusion.

HIV prevention clinical trials’ community engagement guidelines: inequality, and ethical conflicts

ABSTRACT In 2004 and 2005, the first clinical trials were launched to investigate the use of tenofovir for HIV prevention in Cambodia, Cameroon, Nigeria and Thailand. Controversies erupted over the ethical integrity of the research protocol. We reflect on the events that led to the controversies and identified that scientific and ethical concerns raised by members of local communities at each of these sites were erased by trialists, causing crisis that led to premature shut down the early PrEP trials. In the aftermath of these trials, the World Health Organisation, UNAIDS, and AVAC developed ethics guidelines intended to recognize the concerns as authentic, and developed guidelines to improve researchers’ engagement of communities in biomedical HIV prevention trial design and implementation. Our findings suggest that the ethics guidelines are limited in its ability to address power inequalities that leads to voice erasures and non-recognition of local competencies. Rather the ethical documents enabled trialists to gain a new sense of authority through the interpretations of ethical research conduct enabling trialists regain power that can further entrench inequality and voice erasures. To address concerns with what seems an intractable problem, we suggested models of engagement for off-shored research may be the option.

A new Bayesian joint model for longitudinal count data with many zeros, intermittent missingness, and dropout with applications to HIV prevention trials

In longitudinal clinical trials, it is common that subjects may permanently withdraw from the study (dropout), or return to the study after missing one or more visits (intermittent missingness). It is also routinely encountered in HIV prevention clinical trials that there is a large proportion of zeros in count response data. In this paper, a sequential multinomial model is adopted for dropout and subsequently a conditional model is constructed for intermittent missingness. The new model captures the complex structure of missingness and incorporates dropout and intermittent missingness simultaneously. The model also allows us to easily compute the predictive probabilities of different missing data patterns. A zero-inflated Poisson mixed-effects regression model is assumed for the longitudinal count response data. We also propose an approach to assess the overall treatment effects under the zero-inflated Poisson model. We further show that the joint posterior distribution is improper if uniform priors are specified for the regression coefficients under the proposed model. Variations of the g-prior, Jeffreys prior, and maximally dispersed normal prior are thus established as remedies for the improper posterior distribution. An efficient Gibbs sampling algorithm is developed using a hierarchical centering technique. A modified logarithm of the pseudomarginal likelihood and a concordance based area under the curve criterion are used to compare the models under different missing data mechanisms. We then conduct an extensive simulation study to investigate the empirical performance of the proposed methods and further illustrate the methods using real data from an HIV prevention clinical trial.

Emerging trends in contraceptive use, transitions and preferences among female sex workers screened for an HIV prevention clinical trial in Kisumu, Kenya: a cross-sectional study

Background: Globally about 210 million women conceive annually and 38% of these pregnancies are unintended. Female sex workers (FSWs) are at increased risk of both unintended pregnancy and acquiring HIV, which could lead to adverse sexual and reproductive health (SRH) outcomes. We sought to assess contraceptive use or non-use, preferences and determinants among a cohort of FSWs screened for an HIV prevention clinical trial in Kisumu, Kenya. Methods: A cross sectional study of healthy FSWs referred for possible recruitment into the Antibody Mediated HIV Prevention (AMP) Study was conducted between December 2016 and September 2018. Potentially eligible participants were screened for HIV and data on social-demographic, contraceptive use and other SRH characteristics were collected. Those not on a method recorded their contraceptive preferences. Results: Data on 210 FSWs with a median age of 24.5 years (interquartile range, IQR 22-26) are presented. Of these, 187 (89.1%) had two children or fewer; only 56 (26.7%) had completed secondary or higher education. At the time of the interview, 18 (8.6%) were HIV-infected and 181 (86.2%) were using a modern contraceptive. Implants (48.6%) and depot injections (37.6%) were the most commonly used methods. Most (41.4%) of those not on family planning preferred oral pills. Respondents who had two or more children were three times more likely than their primiparous and nulliparous counterparts to report use of a contraceptive. Use of modern contraception methods did not differ by respondent’s ownership of a medical insurance cover or other occupation. Conclusion: There is high use of modern contraception among FSWs in Kisumu with the majority using subdermal implants. Reproductive health programs should implement targeted SRH interventions for specific populations and risk groups. Effective contraceptive counselling and interventions among FSWs should consider the client’s parity and level of education.

Reaching at-risk women for PrEP delivery: What can we learn from clinical trials in sub-Saharan Africa?

IntroductionARV-based pre-exposure prophylaxis (PrEP) has the potential to avert many new HIV infections, yet little is known about how to reach women at high risk for HIV infection and motivate them to initiate PrEP. Clinical trials have succeeded in recruiting at-risk participants, evidenced by control arm HIV incidence ≥3% (defined by the World Health Organization as “substantial risk”). We examined experiences from HIV prevention trials to document recruitment strategies and identify practical, potentially effective strategies for reaching women in real-world PrEP delivery.MethodsWe conducted semi-structured qualitative phone interviews with 31 staff from five countries who had worked on one or more of seven ARV-based HIV prevention clinical trials. Questions explored recruitment strategies used to reach women at risk of HIV and to successfully communicate about PrEP (inclusive of oral and vaginal formulations). We structurally coded data in NVivo and analyzed codes to derive themes. We conducted results interpretation webinars with research and programmatic stakeholders to validate findings and develop recommendations.ResultsClinical trial researchers employed a range of recruitment strategies to recruit at-risk women. They recommended engaging the local community and potential PrEP users via community events, meetings with gatekeepers, and use of community advisory boards; and they encouraged interpersonal communication like presentations in waiting rooms and door-to-door recruitment to address personal concerns and prevent misinformation. Participants also stressed the importance of addressing the challenges that already exist within the health system to create a more enabling environment and delivering positive messages through a variety of communication channels to normalize PrEP.ConclusionsFindings from this study provide important insights into potentially effective ways for countries currently rolling out oral PrEP to reach at-risk women with information about PrEP and promote uptake.

PO 8515 CAPACITY BUILDING IN PREPARATION FOR AN HIV VACCINE TRIAL: THE GLOBALLY RELEVANT AIDS VACCINE EUROPE-AFRICA TRIALS PARTNERSHIP (GREAT)

BackgroundThe Globally Relevant AIDS Vaccine Europe-Africa Trials (GREAT) partnership is an EDCTP-funded project that aims to foster collaboration between institutions in Europe and sub-Saharan Africa to build capacity among African clinical research centres (CRCs) for the design and conduct of HIV-1 vaccine efficacy trials.MethodsIn January 2017, the University of Oxford (UOXF) and five CRCs in Kenya, Uganda and Zambia were awarded a 5 year grant for capacity building and to support conduct of an HIV-1 vaccine trial in different high-risk populations across Africa using cross-clade (conserved protein regions) T-cell vaccines. UOXF and CRCs embarked on activities to strengthen capacity of the CRCs for future efficacy trials. This included training, community engagement, cohort preparation and infrastructure upgrade.ResultsIn the first year, the African investigators at the CRCs collaborated on the development of a protocol aimed at assessing the safety and immunogenicity of the tHIVconsvX vaccines. In preparation for the planned vaccine trial, infrastructure upgrades were prioritised at all partner sites and this included building laboratory space and procurement of appropriate laboratory equipment. Planned infrastructure upgrades will also ensure that high-risk populations can be safely and confidentially included in HIV prevention clinical trials. Systematic community engagement was implemented at all sites, training in GCP/GCLP was provided and training is planned for nominated CRC staff to lead community engagement efforts.ConclusionImproved infrastructure and the provision of targeted training will enhance future trials and increase the capacities of CRCs and staff to conduct quality trials in previously hard-to-reach populations. Early collaboration between investigators from European and sub-Saharan African institutions, with equal responsibilities in the protocol development process, established a meaningful partnership. EDCTP funding also offers a unique opportunity for capacity building.

Feasibility and Safety of IUD Insertion by Mid-Level Providers in Sub-Saharan Africa.

The copper IUD is safe and effective, but underutilized in Sub-Saharan Africa, in part because of a lack of trained providers. The World Health Organization recommends training mid-level providers-including nurses and midwives-to insert IUDs; however, the safety of such task shifting has not been evaluated in Sub-Saharan Africa. Data were drawn from baseline surveys and study charts of 535 sexually active women aged 18-45 who used a copper IUD while participating in an HIV-prevention clinical trial conducted from August 2012 through June 2015 in Malawi, South Africa, Uganda and Zimbabwe. IUDs were inserted by study physicians, nurses and midwives trained as part of the trial, and by local nonstudy providers. Chi-square and Fisher's exact tests were used to compare women's experiences of adverse events-such as irregular bleeding, pelvic pain or device expulsion-by provider type. Half (54%) of women reported experiencing an adverse event; the most common were irregular bleeding and pelvic pain (45% and 25%, respectively). Compared with women who had received an IUD from a study physician or study nurse, greater proportions of women who had received one from a nonstudy provider reported any adverse event (76% vs. 49% and 51%, respectively), irregular bleeding (57% vs. 41% and 45%) and pelvic pain (35% vs. 15% and 32%); the difference between study physicians and nurses was significant only for pelvic pain. Expulsion rates were comparable for study nurses and nonstudy providers (12.3 and 11.9 per 100 woman-years, respectively), but lower for study physicians (7.3 per 100 woman-years). The findings support task shifting of IUD insertion to mid-level providers to improve IUD access in Sub-Saharan Africa.

Optimizing adherence in HIV prevention product trials: Development and psychometric evaluation of simple tools for screening and adherence counseling.

BackgroundLow adherence in recent HIV prevention clinical trials highlights the need to better understand, measure, and support product use within clinical trials. Conventional self-reported adherence instruments within HIV prevention trials, often relying on single-item questions, have proven ineffective. While objective adherence measures are desirable, none currently exist that apply to both active and placebo arms. Scales are composed of multiple items in the form of questions or statements that, when combined, measure a more complex construct that may not be directly observable. When psychometrically validated, such measures may better assess the multiple factors contributing to adherence/non-adherence. This study aimed to develop and psychometrically evaluate tools to screen and monitor trial participants’ adherence to HIV prevention products within the context of clinical trial research.Methods and findingsBased on an extensive literature review and conceptual framework, we identified and refined 86 items assessing potential predictors of adherence and 48 items assessing adherence experience. A structured survey, including adherence items and other variables, was administered to former ASPIRE and Ring Study participants and similar non-trial participants (n = 709). We conducted exploratory factor analyses (EFA) to identify a reduced set of constructs and items that could be used at screening to predict potential adherence, and at follow-up to monitor and intervene on adherence. We examined associations with other variables to assess content and construct validity. The EFA of screener items resulted in a 6-factor solution with acceptable to very good internal reliability (α: .62-.84). Similar to our conceptual framework, factors represent trial-related commitment (Distrust of Research and Commitment to Research); alignment with trial requirements (Visit Adherence and Trial Incompatibility); Belief in Trial Benefits and Partner Disclosure. The EFA on monitoring items resulted in 4 Product-specific factors that represent Vaginal Ring Doubts, Vaginal Ring Benefits, Ring Removal, and Side Effects with good to very good internal reliability (α = .71-.82). Evidence of content and construct validity was found; relationship to social desirability bias was examined.ConclusionsThese scales are easy and inexpensive to administer, available in several languages, and are applicable regardless of randomization. Once validated prospectively, they could (1) screen for propensity to adhere, (2) target adherence support/counselling, and (3) complement biomarker measures in determining true efficacy of the experimental product.

‘Hold on’ (Bambelela)! Lyrical interpretations of participation in an HIV prevention clinical trial

During a five-day workshop, former clinical trial participants and local musicians wrote the lyrics and recorded a song about an HIV prevention trial. Born of concerns about misconceptions regarding experimental drug trials, the aim was to engender engagement with medical researchers and open dialogue about the risks and benefits of trial participation. Composing lyrics that highlighted their credibility as communicators of medical scientific knowledge and their selfless sacrifice to stem the transmission of HIV, women performed their social positioning and cultural authority in contrast to men as well as other women not part of the trial. While involvement in HIV prevention initiatives often attracts stigma, scorn and criticism, the song’s lyrics highlighted women’s new-found identities as heroines searching for a solution to the spread of HIV, challenging these stereotypes. Methodologically, the paper describes a novel approach that uses artistic expression for public engagement with biomedical research.