Assessing the acceptability of, adherence to and preference for a dual prevention pill (DPP) for HIV and pregnancy prevention compared to oral pre-exposure prophylaxis (PrEP) and oral contraception taken separately: protocols for two randomised, controlled, cross-over studies in South Africa and Zimbabwe.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) is a highly effective HIV prevention method; however, uptake and persistence have been low among southern African women. A dual prevention pill (DPP) that combines PrEP with oral contraception (OC) may increase PrEP use and better meet women's sexual and reproductive health needs. We will gauge the DPP's acceptability in two cross-over clinical trials. METHODS AND ANALYSIS: PC952 (Zimbabwe) and PC953 (South Africa) will compare acceptability, adherence and preference for an over-encapsulated DPP versus PrEP and OCs taken separately. HIV-negative, non-pregnant cisgender females in Johannesburg, South Africa (n=96, 16-40 years) and Harare, Zimbabwe (n=30, 16-24 years) will be randomised 1:1 to the order of regimens-DPP or two separate tablets-each used for three 28-day cycles, followed by a 6-month choice period in South Africa. Monthly clinic visits include HIV and pregnancy testing; safety assessments and risk reduction and adherence counselling. We will assess adherence (monthly) based on tenofovir diphosphate drug levels in dried blood spots and by self-report. We will evaluate acceptability (monthly) and preference (end of cross-over) via computer-assisted self-interviewing and in-depth interviews with a subset of participants. Data collection started in September 2022 and ended in January 2024. ETHICS AND DISSEMINATION: PC952 was approved by the Ministry of Health and Child Care, Medical Research Council, Research Council and Medicines Control Authority of Zimbabwe; the Chitungwiza City Health Ethics Committee; and the Joint Research Ethics Committee for the University of Zimbabwe Faculty of Medicine and Health Sciences and Parirenyatwa Group of Hospitals. PC953 was approved by the South African Health Products Regulatory Authority and the University of the Witwatersrand's Human Research Ethics Committee. The Population Council IRB approved both studies. We will disseminate results in open-access journals, clinical trials registries, and at local and international meetings and conferences. TRIAL REGISTRATION NUMBERS: NCT04778514, NCT04778527.

Preventing HIV and achieving pregnancy among HIV sero-different couples: Pilot study of a safer conception intervention in Zimbabwe.

Safer conception services are needed to minimize HIV transmission among HIV sero-different couples desiring pregnancy. Few studies have evaluated the choices couples make when offered multiple safer conception methods or real-world method acceptability and effectiveness. We piloted a comprehensive safer conception program (Clintrials.gov identifier: NCT03049176) for HIV sero-different couples planning pregnancy in Zimbabwe to measure feasibility, method uptake, acceptability, pregnancy outcome, and HIV transmission. This study was not designed to compare rates of HIV transmission by safer conception method choice but rather to understand choices couples make when seeking to minimize risk of HIV transmission and maximize likelihood of pregnancy. Couples in this prospective, non-randomized study were given a choice of one or more currently available safer conception methods: antiretroviral therapy (ART) with monthly viral load (VL) monitoring for the HIV-positive partner (ART/VL), pre-exposure prophylaxis (PrEP) for the HIV-negative partner, vaginal insemination (VI) for couples with an HIV-positive woman, and semen washing (SW) for couples with an HIV-positive man. Couples were followed monthly for up to 12 months of pregnancy attempts, quarterly during pregnancy, and 12 weeks post-partum. At each visit, data on method use, urine for pregnancy testing, and blood for HIV antibody testing, or viral load if HIV-positive, were obtained. Infants born to HIV-positive women were tested for HIV at 6 and 12 weeks. Between March 2017 and June 2019, 46 individuals from 23 HIV sero-different partnerships were enrolled and followed. At enrollment, all couples chose ART/VL, and all couples chose at least one additional method; 74% chose PrEP, 36% chose SW, and 25% chose VI. During pre-pregnancy follow-up visits, three couples discontinued SW, and one couple discontinued VI; all four of these couples opted for ART/VL plus PrEP. Satisfaction with safer conception methods was high among those who chose ART/VL and PrEP. Twelve couples achieved pregnancy. There were no cases of HIV transmission to partners, and no infants tested positive for HIV. This safer conception program is feasible and acceptable, allowing sero-different couples to safely achieve pregnancy. Sero-different couples in Zimbabwe seek a combination of HIV prevention methods, particularly ART/VL plus PrEP. Trial Registration: Clintrials.gov, NCT03049176.

Couples' decision making regarding the use of multipurpose prevention technology (MPT) for pregnancy and HIV prevention.

We conducted a secondary analysis of discrete choice experiment (DCE) data from 395 couples enrolled in the Microbicide Trials Network (MTN)-045/CUPID study in Uganda and Zimbabwe to understand couple decision making around choice of multipurpose prevention technologies (MPTs) to prevent both HIV and pregnancy. Members of couples completed the same DCE, first separately then jointly, choosing between two hypothetical MPTs in a series of nine questions. Most couples either had similar preferences at the outset or had equal decision-making around MPTs (62%). Couples with male influence (17%) were more likely to use contraceptive pills with a male partner's knowledge and couples with female influence (21%) were less likely to have shared decision making about family planning. Males influenced discussion around MPT duration, side effects, menstrual changes, and how the vagina feels during sex. Decision making was relatively shared, though decisions around certain attributes were more likely to be dominated by male partners.

Understanding the role of men in women's use of the vaginal ring and oral PrEP during pregnancy and breastfeeding: multi-stakeholder perspectives.

We examined men's influence on women's interest in biomedical HIV prevention during pregnancy and breastfeeding through structured questionnaires and focus group discussions with currently or recently pregnant and breastfeeding (P/BF) women (n = 65), men with P/BF partners (n = 63) and mothers/mothers-in-law of P/BF women (n = 68) in eastern and southern Africa. Data were transcribed, coded and summarised into analytical memos. Men were depicted by most participants as joint decision-makers and influencers of women's use of HIV prevention. Cultural and religious norms depicting men as heads, breadwinners and protectors of the family were cited to legitimise their involvement in decision-making. Male partner education and engagement were recommended to garner their support in women's HIV prevention. This study elucidates how P/BF women's ability to prevent HIV is shaped by traditional and contemporary gender norms in social settings and locations where the study was conducted. Findings may aid intervention design to engage men for P/BF women's effective use of microbicide and oral PrEP.

Making the Case for Joint Decision-Making in Future Multipurpose Prevention Technology (MPT) Choice: Qualitative Findings on MPT Attribute Preferences from the CUPID Study (MTN-045).

INTRODUCTION: Young women in sub-Saharan Africa account for two-thirds of all new HIV infections and face high rates of unintended pregnancy. Multipurpose prevention technologies (MPTs) are promising products under development that are designed to simultaneously prevent HIV and unintended pregnancy. Since MPTs will be used in the context of sexual relationships, ensuring acceptability and use requires understanding the role of male partners in MPT use decision-making. METHODS: This paper draws on qualitative data from 39 couples enrolled in the Microbicide Trials Network (MTN) 045 study, conducted in 2019-2020. Partners completed a discrete choice experiment (DCE), first separately and then jointly, to measure preferences for future MPT attributes and then completed a qualitative interview. We also draw on quantitative data from interviewer observation about who dominated the decision-making process during the joint DCE. Content analysis was used to examine (1) how couples made decisions on existing non-MPT HIV and pregnancy prevention products; (2) how couples made decisions on future ideal-MPT product during the DCE; and (3) how these decision-making processes varied by decision-making dominance (10 male, 10 female and 19 equal) and interview type (19 joint and 20 separate). RESULTS: Existing non-MPT product decisions focused on trust between partners and product attributes, while future ideal-MPT product decisions exclusively focused on product attributes. Across existing and future products, preferences for product attributes varied by gender. Male partners were most concerned with limiting side effects impacting sexual pleasure, female partners were most concerned with limiting side effects causing physical symptoms and both were concerned with the return to fertility. Across all dominance and interview types, couples reported making decisions together and female partners were often able to negotiate with male partners for their preferred product or set of product attributes. CONCLUSIONS: Research activities in this study provided an opportunity for couples to openly present their product attribute preferences to their partner, learn about their partner's attribute preferences, negotiate for their ideal set of attributes and ultimately choose attributes that benefited the couple without disempowering the female partner. Future research should focus on the utility of couple-based decision-making aids or similar tools for facilitating joint MPT decision-making.

''Ask the way from those who have walked it before"-Grandmothers' roles in health-related decision making and HIV pre-exposure prophylaxis use among pregnant and breastfeeding women in sub-Saharan Africa.

HIV acquisition among pregnant and breastfeeding women in sub-Saharan Africa and vertical transmission rates remain high despite established strategies for HIV prevention. During the MTN-041/MAMMA study, we explored the influence of grandmothers (mothers and mothers-in-law of pregnant and breastfeeding women) in eastern and southern Africa on the health-related decisions of pregnant and breastfeeding women and their potential to support use of HIV prevention products. To do this we used structured questionnaires and focus group discussions with three stakeholder groups: 1) grandmothers, 2) HIV-uninfected currently or recently pregnant or breastfeeding women and 3) male partners of currently or recently pregnant or breastfeeding women. A total of 23 focus group discussions comprising 68 grandmothers, 65 pregnant or breastfeeding women and 63 male partners were completed across four study sites. Grandmothers were described as important sources of information during pregnancy and breastfeeding playing both supportive and influencer roles due to personal maternal experience and generational knowledge. While pregnant and breastfeeding women were not keen to involve grandmothers in HIV prevention decision making, they were accepting of grandmothers' involvement in a supportive role. Grandmothers expressed willingness to support pre-exposure prophylaxis use and agreed with the other two stakeholder groups that this decision should be made by women themselves or together with partners. These novel data indicate potential for grandmothers' health related supportive roles to be extended to support decision-making and adherence to biomedical HIV prevention options, and possibly contribute to the decline in HIV acquisition among pregnant and breastfeeding women in these communities.

Couples' Preferences for "2 in 1" Multipurpose Prevention Technologies to Prevent Both HIV and Pregnancy: Results of a Discrete Choice Experiment in Uganda and Zimbabwe.

End-user input early in biomedical product development may optimize design to support high uptake and adherence. We interviewed 400 couples (800 total participants) in Uganda and Zimbabwe to assess their preferences for multipurpose prevention technologies (MPTs) for HIV and pregnancy prevention. Using a discrete choice experiment, couples made a series of choices between hypothetical MPTs, including oral tablets and vaginal rings, inserts, and films and completed an interviewer-administered questionnaire assessing sociodemographic and behavioral measures. Most couples preferred presented MPTs over male condoms. Couples' MPT choices in both countries were influenced most by the combination of product form and dosing frequency, with monthly dosing preferred over daily. Analysis highlighted differences by country as to which side effects were most important: Ugandan couples placed greater importance on effects on the vaginal environment during sex, whereas Zimbabwean couples placed more importance on changes to menstruation and other side effects (headache, cramps). Couples' preferences signaled an openness to new product forms and more frequent dosing if preferred characteristics of other attributes were achieved.

Religious leaders' role in pregnant and breastfeeding women's decision making and willingness to use biomedical HIV prevention strategies: a multi-country analysis.

Oral Pre-Exposure Prophylaxis (PrEP) is an established option, and the dapivirine vaginal ring is emerging as a promising strategy for HIV prevention option for women. Because of this, understanding the contextual and cultural factors that will support the increased uptake of these products is crucial. In sub-Saharan Africa, religious leaders may be important stakeholders to involve in product information, education and roll-out. We conducted a sub-analysis of data from 232 participants taking part in the MTN-041/MAMMA study to explore religious leaders' involvement in pregnant and breastfeeding women's health. Study participants viewed biomedicine and spirituality as interlinked and believed that women could seek health-related care from medical experts and turn to faith-based organisations for religious or spiritual needs. Religious leaders were invested in the health of their congregations, endorsed a variety of sexual health strategies, and were eager to learn more about emerging HIV prevention technologies. These data signal the role of religious leaders in supporting their communities, and the importance of involving religious leaders in efforts to roll out new HIV prevention products to facilitate uptake.

Sexual Attitudes, Beliefs, Practices, and HIV Risk During Pregnancy and Post-delivery: A Qualitative Study in Malawi, South Africa, Uganda, and Zimbabwe.

Women who acquire HIV during the pregnancy and breastfeeding periods have a higher risk of transmitting the virus to their child than women who become infected with HIV before pregnancy. We explore the context of sexual beliefs and practices that may shape both HIV risk and willingness to use HIV prevention products during pregnancy and postpartum in Malawi, South Africa, Uganda and Zimbabwe. Twenty-three single sex focus group discussions and 36 in-depth interviews took place between May and November 2018 with recently pregnant or breastfeeding women, men, mothers and mothers-in-law of pregnant or breastfeeding women, and key informants. Participants across study groups and sites (N = 232) reported various perceived benefits and harms of sex during pregnancy and postpartum. Participants discussed reasons why men might seek sex outside of the relationship. There is a critical need for alternative prevention options to protect pregnant and breastfeeding women from HIV.

Impact and experience of participant engagement activities in supporting dapivirine ring use among participants enrolled in the phase III MTN-020/ASPIRE study.

BACKGROUND: Low adherence to investigational products can negatively impact study outcomes, limiting the ability to demonstrate efficacy. To continue advancing potential new HIV prevention technologies, efforts are needed to improve adherence among study participants. In MTN-020/ASPIRE, a phase III randomized, double-blind, placebo-controlled study of the dapivirine vaginal ring carried out across 15 sites in sub-Saharan Africa, a multifaceted approach to adherence support was implemented, including a strong focus on participant engagement activities (PEAs). In this manuscript, we describe PEAs and participant attendance, and analyze the potential impact of PEAs on ring use. METHODS: All sites implemented PEAs and submitted activity and attendance reports to the study management team throughout the study. Participant demographics were collected via case report forms. Residual dapivirine remaining in the last ring returned by each participant was used to estimate drug released from the ring, which was then adjusted for time participants had the ring to calculate probable use categorized into three levels (low/intermittent/high). Product use was connected to PEA attendance using participant identification numbers. We used multivariate Poisson regression with robust standard errors to explore differences in ring use between PEA attendance groups and reviewed qualitative reports for illustrative quotes highlighting participant experiences with PEAs. RESULTS: 2312 of 2629 study participants attended at least one of 389 PEAs conducted across sites. Participant country and partner knowledge of study participation were most strongly associated with PEA attendance (p < 0.005) with age, education, and income status also associated with event attendance (p < 0.05). When controlling for these variables, participants who attended at least one event were more likely to return a last ring showing at least some use (RR = 1.40) than those who never attended an event. There was a stronger correlation between a last returned ring showing use and participant attendance at multiple events (RR = 1.52). CONCLUSIONS: Our analysis supports the growing body of work illustrating the importance of meaningfully engaging research participants to achieve study success and aligns with other analyses of adherence support efforts during ASPIRE. While causation between PEA attendance and product use cannot be established, residual drug levels in returned rings strongly correlated with participant attendance at PEAs, and the benefits of incorporating PEAs should be considered when designing future studies of investigational products.

Application of a Body Map Tool to Enhance Discussion of Sexual Behavior in Women in South Africa, Uganda, and Zimbabwe.

Body mapping methods are used in sexual and reproductive health studies to encourage candid discussion of sex and sexuality, pleasure and pain, sickness and health, and to understand individuals' perceptions of their bodies. VOICE-D, a qualitative follow-up study to the VOICE trial, developed and used a body map tool in the context of individual in-depth interviews with women in South Africa, Uganda, and Zimbabwe. The tool showed the outline of a nude female figure from the front and back perspective. We asked women to identify, label, and discuss genitalia and other body parts associated with sexual behaviors, pain, and pleasure. Respondents could indicate body parts without having to verbalize potentially embarrassing anatomical terms, enabling interviewers to clarify ambiguous terminology that may have otherwise been open to misinterpretation. Body maps provided women with a non-intimidating way of discussing and disclosing their sexual practices, and minimized miscommunication of anatomical and behavioral terminology.

Preferences and Acceptability of Vaginal Delivery Forms for HIV Prevention Among Women, Male Partners and Key Informants in South Africa and Zimbabwe: Qualitative Findings.

The attributes of an HIV microbicide may affect its acceptability, uptake and use. Quatro, a clinical study with a qualitative component, was conducted to elicit input from end-users and key informants (KIs) on four different placebo vaginal microbicide delivery forms; fast dissolving insert, ring, film and gel. In-depth interviews and focus group discussions were conducted with young women, their male partners and KIs, to explore acceptability and preferences of the four placebo products, with the intention of improving product attributes, adherence, and consequently, long term effectiveness. None of the four microbicide delivery forms stood well above others as the most preferred. Product attributes; long-action, ease of use, invisibility, female initiated and non-interference during sex were favourable in both countries. Despite preference for the long-action, on-demand products were the most liked by women. Qualitative data from the Quatro study provided rich feedback on specific attributes important to the acceptability of four HIV prevention product platforms currently in development, enabling more informed and guided product development efforts moving forward.

Influences on willingness to use vaginal or oral HIV PrEP during pregnancy and breastfeeding in Africa: the multisite MAMMA study.

INTRODUCTION: Women in sub-Saharan Africa spend a substantial portion of their reproductive lives pregnant and/or breastfeeding (P/BF), yet they have limited options to prevent HIV during these maternal stages. In preparation for phase 3b prevention trials in P/BF women, we explored attitudes about using a vaginal ring or oral pills for pre-exposure prophylaxis (PrEP), perceptions of HIV risk during P/BF and key influences on future PrEP use. METHODS: In 2018, we conducted 16 single-sex focus group discussions (FGDs) with community- and clinic-recruited HIV-uninfected women, currently or recently P/BF, aged 18 to 40, and men with (currently or recently) P/BF partners, aged 18+. Participants completed a behavioural questionnaire, viewed an educational video and handled prototype placebo products. FGDs were conducted in local languages and transcribed, coded and analysed, using a socio-ecological framework, for key influences on willingness to use products, HIV risk perceptions and opinions on product attributes. RESULTS: Of the 128 participants (65 women, 63 men) 75% lived with their partner and 84% had a child. Women reported the most important influencers when P/BF were partners, and all stated that health decisions when P/BF are typically made jointly (e.g. medication use; ante/postnatal and baby care). There was consensus that P/BF women are at high risk for HIV, primarily because of their partner's infidelities, and new prevention options were welcomed. Participants valued multiple options and stated that woman's personal preference would be key to product choice. Anticipated concerns about products included risk of miscarriage, impact on infant development, complications during delivery and adequate production or taste of breastmilk. Specific perceived disadvantages emerged for the ring (e.g. vaginal discomfort, difficulty inserting/removing) and for pills (e.g. nausea/vomiting) that may be exacerbated during pregnancy. Health care providers' (HCPs) knowledge and approval of product use during P/BF was needed to mitigate anticipated fears. CONCLUSIONS: Participants perceived pregnancy and breastfeeding as high HIV risk periods and valued new prevention options. HIV protection of the mother-child dyad, safety of the baby, and ultimately, health of the family were paramount. Endorsement by HCPs and support from partners were key to future product acceptance. Participants recommended involving partners and HCPs in sensitization efforts for future trials.

"The state of mind tells me it's dirty": menstrual shame amongst women using a vaginal ring in Sub Saharan Africa.

Socio-cultural beliefs and practices surrounding menses influence women's sexual and reproductive health behaviors and decision-making. We analyzed menstrual experiences within the context of the MTN-020/ASPIRE clinical trial during which women were asked to use a monthly vaginal ring for HIV prevention. The qualitative component of the trial was conducted during February 2013-June 2015, included interviews and focus group discussions with 214 women aged 18-42, in Malawi, Zimbabwe, Uganda, and South Africa. Emotions of shame, embarrassment and disgust relating to menses emerged. Menstruation was referred to using euphemistic terms or language about dirtiness. Women were uncomfortable touching their own menstrual blood when removing vaginal rings and felt embarrassed about study staff seeing blood on returned rings. Despite reassurances, women felt ashamed performing study procedures while menstruating, leading to missed study visits. Women's aversion to menstrual blood was linked to narratives about avoiding sex during menses and beliefs about its potential harms. Women associated men's disgust pertaining to menstrual blood with men's willingness to use condoms for sex only during menses, highlighting another way through which socio-cultural beliefs and practices around menstruation affect HIV protective behaviours. These findings provide novel insight into menstrual shame among women in these four countries.

Acceptability of a long-acting injectable HIV prevention product among US and African women: findings from a phase 2 clinical Trial (HPTN 076).

INTRODUCTION: High HIV incidence and low adherence to daily oral PrEP among women underscore the need for more acceptable and easier to use HIV prevention products. Global demand for injectable contraception suggests that new, long-acting, injectable formulations could meet this need. We examine acceptability of a long-acting injectable PrEP among HIV-uninfected women in Zimbabwe, South Africa and two United States phase 2 trial sites. METHODS: Quantitative surveys were administered at the first, fourth and sixth injection visits. Focus group discussions (FGD) were conducted after the sixth injection visit. We compared the acceptability of injectable product attributes, prevention preferences and future interest in injectable PrEP by site and arm and ran longitudinal ordinal logistic regression models to identify determinants of future interest in injectable PrEP. RESULTS: Between April 2015 and February 2017, the trial enrolled 136 (100 African, 36 US) women with a median age of 31 years. Most participants (>75%) rated injectable attributes as very acceptable. While few reported rash or other side effects, 56% to 67% reported injection pain, with nonsignificant differences over time and between arms. During FGDs, participants described initial fear of the injectable and variable experiences with pain. Most US and African participants preferred injectable PrEP to daily oral pills (56% to 96% vs. 4% to 25%). Future interest in using injectable PrEP was associated with acceptability of product attributes and was higher in African than US sites. In FGDs, participants described multiple reasons for trial participation, including a combination of monetary, health-related and altruistic motivations. While associated with future interest in use in univariate models, neither altruistic nor personal motivations remained significant in the multivariate model. CONCLUSIONS: This study found that long-acting injectable PrEP is acceptable among African and US women experiencing product use. Acceptability of product attributes better predicted future interest in injectable use than experience of pain. This is reassuring as a single-dose regimen of a different product has advanced to phase 3 trials. Finally, the study suggests that future demand for an injectable PrEP by women may be greater in African than US settings, where the risk of HIV is highest.

End-user preference for and choice of four vaginally delivered HIV prevention methods among young women in South Africa and Zimbabwe: the Quatro Clinical Crossover Study.

INTRODUCTION: Adherence to HIV prevention methods is a challenge, particularly for young women in Sub-Saharan Africa. End-user research during product development can inform modifiable factors to increase future uptake and adherence. METHODS: Preferences for four vaginally inserted placebo HIV prevention methods were assessed among Zimbabwean and South African young women using a crossover clinical design. For each of months 1 to 4, participants were asked to use a pre-coitally inserted film, insert (vaginal tablet) and gel once/week for a month, and a monthly ring in a randomly assigned sequence. Participants subsequently chose one preferred product to use as directed for the final study month. Women ranked the four products from most preferred to least preferred at enrolment and after trying all products. RESULTS: A total of 200 women aged 18 to 30 (mean 23) were enrolled; 178 (89%) completed follow-up. At baseline, 41% of participants selected the gel as their most preferred product and 61% selected the ring as least preferred. During the crossover period, most (82% to 85%) self-reported using each product at least once a week, although only half the time with sex. Objective biomarker data confirmed adequate use of all products. After trying each product, rankings changed with the film, ring, insert and gel being selected by 29%, 28%, 26% and 16% respectively. Choice varied significantly by country (p < 0.001): More Zimbabweans chose the film (45%), and more South Africans chose the insert (34%). Among women choosing the ring, 88% reported using it every time with sex. By contrast, self-reported adherence was lower for "on-demand" (coitally associated) products, with 40% to 55% using them every time during sex (p < 0.001). CONCLUSIONS: Preferences for these four dosage forms varied before and after use, and both within and across countries - there was no clear favourite - indicating the need for a range of options for end-users The ring's popularity increased the most with use, was the second most preferred delivery system, and per self-report, provided more coverage during sex. These end-user perspectives provide important information to product developers and funding agencies.

Negative rumours about a vaginal ring for HIV-1 prevention in sub-Saharan Africa.

Rumours may influence health-related behaviours, including the uptake of and adherence to HIV prevention products. This study assessed the safety and effectiveness of a vaginal ring delivering the antiretroviral dapivirine for HIV prevention in Africa. We explored negative rumours about study participation and the vaginal ring amongst study participants and their communities in Malawi, Uganda, South Africa and Zimbabwe. In total 214 women participated in either single or serial in-depth interviews, or a focus group discussion. Three key findings emerged in the data. Firstly, rumours reflected fears concerning the ring and trial participation. Given the historical-political context of the countries in which the trial was conducted, the ring's investigational nature and its foreign origin, ring use was rumoured to cause negative health outcomes such as cancer and infertility and to be associated with practices such as witchcraft or Satanism. The salience of these rumours varied by country. Secondly, rumours reportedly affected participants' adherence to the ring, and other women's willingness to participate in the study. Finally, participants reported that participant engagement activities helped address rumours, resulting in enhanced trust and rapport between staff and participants.

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 (> 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. TRIAL REGISTRATION: NCT02358616 ; Posted February 9, 2015, retrospectively registered.

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.

Misreporting of contraceptive hormone use in clinical research participants.

OBJECTIVE: Researchers traditionally rely on participant self-report for contraceptive use. We hypothesized that self-reported contraceptive use by clinical research participants may disagree with objectively measured hormonal status. STUDY DESIGN: We enrolled women in Harare, Zimbabwe, aged 18-34, who by self-report had not used hormonal or intrauterine contraception for >30 days, or depot medroxyprogesterone acetate for >10 months, into a study designed to assess biologic changes with contraceptive initiation and use. Blood samples obtained at enrollment and each follow-up visit (N=1630 from 447 participants) were evaluated by mass spectrometry for exogenous hormones. We individually interviewed a subset of participants (n=20) with discrepant self-reported and measured serum hormones to better understand nondisclosure of contraceptive use. RESULTS: Discrepant with self-reported nonuse of hormonal contraception, synthetic progestogens were detectable in 120/447 (27%, 95% confidence interval 23%-31%) enrolled women. Measured exogenous hormones consistent with use of contraceptive pills (n=102), injectables (n=20) and implants (n=3) were detected at enrollment, with 7 women likely using >1 contraceptive. In-depth interviews revealed that participants understood the requirement to be hormone free at enrollment (100%). Most (85%) cited partner noncooperation with condoms/withdrawal and/or pregnancy concerns as major reasons for nondisclosed contraceptive use. All interviewed women (100%) cited access to health care as a primary motivation for study participation. Of participants who accurately reported nonuse of hormonal contraception at enrollment, 41/327 (12.5%) had objective evidence of nonstudy progestin use at follow-up that disagreed with self-reported nonuse. CONCLUSIONS: Women joining contraceptive research studies may misrepresent their use of nonstudy contraceptive hormones at baseline and follow-up. Objective measures of hormone use are needed to ensure that study population exposures are accurately categorized. IMPLICATIONS STATEMENT: Among Zimbabwean women participating in a contraceptive research study, 27% had objective evidence of use of nonstudy contraceptives at enrollment that disagreed with self-report. Studies that rely on self-report to identify contraceptive hormone exposure could suffer from significant misclassification.