Understanding women’s motivations to participate in MTN-003/VOICE, a phase 2b HIV prevention trial with low adherence

Background: In biomedical prevention trials, correct and consistent use of the investigational product is crucial to determine efficacy. Product adherence in VOICE, a phase 2B randomized trial of a vaginal gel and oral tablets for HIV prevention, was low (~ 34%), yet self-reported adherence and retention was high (\u3e 90%). This analysis from VOICE-D, a post-trial qualitative ancillary study, explores motivations to participate in VOICE, and possible sources of misalignment between the stated priorities of the trial and the participants. Methods: VOICE-D enrolled 171 former VOICE participants to investigate, among other things, reasons for joining and remaining in the trial. Local language in-depth interviews and focus groups were transcribed and translated into English and coded and analyzed using NVivo. Data on motivation to join obtained from a VOICE termination visit survey of 106 participants were also analyzed to corroborate the VOICE-D findings. Results: Participants primarily participated for personal health benefits (e.g. free healthcare and HIV testing) and reported remaining enrolled from a sense of commitment to the trial. Altruistic motivations were the most commonly stated motivation on the termination visit survey; qualitatively, many of those stating altruistic reasons also desired personal health benefits. Joining for financial reimbursement was not commonly mentioned. Social networks influenced recruitment and spread therapeutic misconception. Conclusions: Women’s participation for personal health benefits highlighted their desire to monitor their HIV risk and overall health. Helping participants view use of investigational products as improving social capital and reminding participants of their study responsibilities may improve trial outcomes. Understanding the reasons for participating in studies will help to ensure alignment between priorities of researchers and participants

Misreporting of product adherence in the MTN-003/VOICE trial for HIV prevention in Africa: Participants’ explanations for dishonesty

Consistent over-reporting of product use limits researchers’ ability to accurately measure adherence and estimate product efficacy in HIV prevention trials. While lying is a universal characteristic of the human condition, growing evidence of a stark discrepancy between self-reported product use and biologic or pharmacokinetic evidence demands examination of the reasons research participants frequently misrepresent product use in order to mitigate this challenge in future research. This study (VOICE-D) was an ancillary post-trial study of the vaginal and oral interventions to control the epidemic (VOICE) phase IIb trial (MTN 003). It was conducted in three African countries to elicit candid accounts from former VOICE trial participants about why actual product use was lower than reported. In total 171 participants were enrolled between December 2012 and March 2014 in South Africa (n = 47), Uganda (n = 59) and Zimbabwe (n = 65). Data suggested that participants understood the importance of daily product use and honest reporting, yet acknowledged that research participants typically lie. Participants cited multiple reasons for misreporting adherence, including human nature, self-presentation with study staff, fear of repercussions (study termination resulting in loss of benefits and experience of HIV-related stigma), a permissive environment in which it was easy to get away with misreporting, and avoiding inconvenient additional counseling. Some participants also reported mistrust of the staff and reciprocal dishonesty about the study products. Many suggested real-time blood-monitoring during trials would encourage greater fidelity to product use and honesty in reporting. Participants at all sites understood the importance of daily product use and honesty, while also acknowledging widespread misreporting of product use. Narratives of dishonesty may suggest a wider social context of hiding products from partners and distrust about research, influenced by rumors circulating in clinic waiting-rooms and surrounding communities. Prevailing power hierarchies between staff and participants may exacerbate misreporting. Participants recognized and suggested that objective, real-time feedback is needed to encourage honest reporting

How presentation of drug detection results changed reports of product adherence in South Africa, Uganda and Zimbabwe

Accurate estimates of study product use are critical to understanding and addressing adherence challenges in HIV prevention trials. The VOICE trial exposed a significant gap between self-reported adherence and drug detection. The VOICE-D qualitative study was designed to better understand non-adherence during VOICE, and was conducted in 2 stages: before (stage 1) and after (stage 2) drug detection results were provided to participants. Transcripts from 44 women who participated in both stages were analysed to understand the effect of presenting drug detection data on narratives of product use. Thirty-six women reported high adherence in stage 1, yet admitted non-use in stage 2, three reported high adherence in both stages (contrary to their drug detection results) and five had consistent responses across both stages and drug results. Presenting objective measures of use may facilitate more accurate product use reporting and should be evaluated in future prevention trials