Male Partner Opinions of the Dapivirine Vaginal Ring Used During an Open-Label Extension HIV Prevention Trial in KwaZulu-Natal, South Africa.

BACKGROUND: The dapivirine vaginal ring ("the ring") reduced HIV acquisition by about 35% in phase III trials, with modeling from open-label extension trials estimating 50% HIV protection with consistent use. The ring may be used without male partner knowledge. The Assessment of ASPIRE and HOPE Adherence (AHA) substudy aimed to understand the impact of sociocontextual issues on ring adherence. This subanalysis provides insight into disclosure and male partner influence on ring acceptability. METHODS: Data were collected using 4 focus group discussions with 18 male partners of phase III trial participants at 2 sites in KwaZulu-Natal, South Africa. Qualitative data were coded, summarized by urban vs. rural location, and analyzed thematically. RESULTS: Male partners aged 23-49 years wanted to be informed about the ring use to maintain the trust in their relationships. Their initial response to the ring was characterized by fear due to perceived impact of the ring on their female partner's reproductive system, their penile safety, and that the ring would encourage women to engage in unprotected sex and infidelity. Over time and with information and experience with having a partner who had used the vaginal ring, this fear transformed to support for women to have their own HIV prevention option. CONCLUSION: Male partners supported the ring as an HIV prevention method for women but wanted to be informed about its use. Engaging male partners on female-initiated HIV prevention methods and increased education among rural men may contribute to improved partner support and facilitate women's consistent use.

Ring-ing in the Future: Participant and Male Partner Perspectives Regarding Future Use of the Dapivirine Vaginal Ring for HIV Prevention.

Women account for a disproportionate percentage of new HIV infections in sub-Saharan Africa indicating a need for female-initiated HIV prevention options congruent with their lifestyles. The dapivirine vaginal ring for HIV prevention is one such option. We explored the interest of women, who used this ring during the Microbicide Trials Network's ASPIRE and HOPE studies, in using the ring post-licensure and what they perceived as important considerations for future use. We also explored perspectives of HOPE participants' male partners on their involvement in their partners' future ring use. Women appeared keen to use the ring in the future and expressed desires for easy access, support for both ongoing and new users and intense community engagement. In parallel, male partners indicated high levels of interest in supporting their partners' ring use and being involved in ring use decision making. These data offer important insights for ring rollout planning and engagement activities.

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.

Men's Sexual Experiences with the Dapivirine Vaginal Ring in Malawi, South Africa, Uganda and Zimbabwe.

The dapivirine vaginal ring has been well-tolerated and shown to prevent HIV in clinical trials. The ring is female initiated, yet endorsement for use is sought from male partners in many relationships. In clinical studies, participants have expressed worries about men detecting rings during vaginal sex, which introduces concerns about product use disclosure, sexual pleasure, penile harm, inter-partner dynamics, and ring removals. This study reports African men's firsthand sexual experiences with the ring. Qualitative data were captured through 11 focus group discussions and one in-depth interview with 54 male partners of ring-users at six research sites in Malawi, South Africa, Uganda and Zimbabwe. Following a semi-structured guide, and using demonstration rings, vulva and penis models, men were asked to discuss the ring's impact on sex and views on male engagement and ring use. Interviews were facilitated by local male social scientists, audio-recorded, translated into English, and analyzed thematically. 22 (41%) of the male partners reported feeling the ring during sex, often attributed to perceived incorrect insertion. Many men described the ring as "scratching" the tip of their penises, and sensations of "prodding" something that "blocked" the vagina and prohibited "full entry". In most cases, feelings dissipated with time or when sexual fluids increased. Less common descriptions included perceiving the vaginal texture, wetness and size as different, which increased pleasure for some, and decreased for others. Over half (59%) never noticed the ring; some attempting and failing to feel it during intercourse. A majority of men reported that the ring did not lead to changes in sexual positions, feelings, frequency or experience of sex, although some were initially afraid that the ring was a "magic snake" or "potion". Male partners expressed strong opinions that ring use was a shared prevention responsibility that men should be engaged in, especially for maintaining trust and open communication in relationships. The ring was noticed by many male partners, particularly during women's initial stages of ring use, although this led to few sexual problems or changes. Nevertheless, results suggest that risk of ring discovery should be discussed with women to mitigate any potential negative reactions or social harm. Strategies to increase male partner engagement will enhance support of this prevention method for women.

Women design their own vaginal microbicide trial: Suggestions on how to improve adherence from former participants of HIV prevention trials.

Low adherence in vaginal microbicide clinical trials for HIV prevention has impeded interpretation of trial results and hindered evaluation of potentially efficacious HIV prevention gels. Understanding the underlying reasons why women join trials and their barriers to product use can support identification of ways to improve adherence and its reporting. Eight focus group discussion workshops were conducted with 46 former microbicide trial participants in Durban, South Africa and Mwanza, Tanzania. Participants provided feedback on why women join trials, the barriers to using study gel and reporting adherence accurately, and how clinical trial design can be improved to support better adherence and its reporting. Women join microbicide trials for a number of important reasons such as healthcare and financial reimbursement. Fear of adverse effects from the investigational product was the most important reason why participants reported not using the gel. The key reason for inaccurate reporting of gel use was fear of removal from the trial. Participants made concrete suggestions for improving microbicide trial design such as applicator use testing and real time feedback, improving education to participants about how trials answer their research questions, and improving transparency and clarity about study procedures. Participants also gave feedback on an innovative trial design with a non-randomised arm. Identifying HIV prevention products for women requires better understanding of the lives of women asked to join these trials, and application of that understanding to microbicide trial design. This study has demonstrated that participants and research teams can work collaboratively to design clinical trials that meet needs of both the research and of participants.

Qualitative Perceptions of Dapivirine VR Adherence and Drug Level Feedback Following an Open-Label Extension Trial.

BACKGROUND: There continues to be a need for HIV prevention options that women can initiate and use autonomously. The dapivirine vaginal ring (VR) has been shown to have a favorable safety profile and reduce the risk of HIV-1 acquisition. We report on women's experiences with VR adherence during the MTN-025/HIV Open-label Prevention Extension (HOPE) study and responses to Residual Drug Level (RDL) results. SETTING: Ten women at each of the 6 HOPE research sites in Lilongwe, Malawi; Durban (2 sites) and Johannesburg, South Africa; Kampala, Uganda; and Chitungwiza, Zimbabwe, were randomly selected (n = 60). METHODS: After confirmation of eligibility criteria, in-depth interviews were conducted where available RDL results were presented. RESULTS: Many women with low RDL release measurements deflected blame onto other factors (the ring, the drug, and faulty testing machines) and distrust of the testing method. The disclosure of RDL results enabled some users to discuss their challenges experienced (fear of partner objections, perceived side effects, and removals during menses). Consistent users reported important motivators (support from others, protection from HIV, and enhanced sexual experiences from the VR). CONCLUSION: The VR provided a sense of security for some women; however, adherence was still challenging for others regardless of it being a female controlled, long-acting HIV prevention technology. Adherence measurements may not be sustainable in the real-world implementation of the VR, although they can be seen as a benefit as they provide a better understanding of actual product use and provide women with a platform to discuss their experiences.

Prevention, Partners, and Power Imbalances: Women's Views on How Male Partners Affected Their Adherence to Vaginal Microbicide Gels During HIV Prevention Trials in Africa.

BACKGROUND: Low adherence has contributed to disappointing results for trials testing vaginal microbicides for HIV prevention. This study engaged former gel trial participants to understand the reasons behind low adherence and seek suggestions on how to improve products and adherence to microbicides. This analysis examines the impact of participant perceptions of male partners on participant adherence and suggestions on how to address those issues. METHODS: Eight focus group discussion workshops were conducted with 46 former microbicide trial participants in South Africa and Tanzania. Participants provided feedback on why women join trials, barriers to using gels and reporting adherence accurately, and how adherence and adherence reporting can be improved. RESULTS: Participants reported that male partners can affect women's ability to use gels. For some, the lubricating effects caused relationship conflicts due to suspicion of male partners about infidelity. Needing to provide sex to partners on demand was a barrier to gel use. Participants suggested a gel formulation which was thicker and less noticeable, and explicit male partner engagement to enhance understanding of the purpose of the gels. CONCLUSIONS: The imbalance of power in intimate relationships affects the ability of women to use microbicides as directed. To improve adherence to HIV prevention methods within trials and for successful rollout of proven HIV prevention methods in populations, it is important that the complicated dynamics of sex and relationships be taken into greater consideration and that women receive targeted support to navigate product use and communication within the context of these gender dynamics.

Perceptions of the "Fabric" - An exploratory study of a novel multi-purpose technology among women in Sub Saharan Africa.

BACKGROUND: HIV and pregnancy prevention are dual health priorities for women, and particularly in sub-Saharan Africa. Drug-eluting fibers offer a dosage form that combines HIV prevention and contraception, but early understanding of end-user perspectives is critical to avoid misalignment between products being developed and preferred product attributes. METHODS: Focus group discussions (FGDs) were conducted in South Africa, Uganda and Zimbabwe, among 55 women who had used vaginal products in previous trials. Participants were given the opportunity to feel a sample of electrospun nanofiber (the fabric), see how it dissolves, and give feedback on shape, size and other attributes. Women were also asked to compare the fabric to vaginal gel and film. RESULTS: Three key themes regarding the acceptability of the fabric emerged: 1) look and feel of the product undissolved vs. undissolved, 2) expected effect on sex, and 3) convenience and ease of use. Upon being presented with the fabric, women were initially distrustful, seeing it as undesirable for vaginal insertion. Women generally approved of the product once they saw it dissolve. However, they stressed the importance of the product not interfering with sex by altering the vaginal environment. Women also reacted favorably to the perceived convenience of the fabric, particularly with regards to storage and transport, perceived ease of insertion and use, and dosing regimen. CONCLUSION: Multipurpose prevention technologies, and nanofibers in particular, should be developed with an eye to minimizing impact on sex while maximizing convenience, and presented in such a way as to emphasize non-abrasiveness and ease of dissolution.

Research participants' skills development as HIV prevention peer educators in their communities.

This article describes the influence of a peer education programme on skills development among 22 women participating in HIV prevention trials. Interviews were used to collect data on peer educator experiences and their opinions of the trainings. The training enhanced their agency and confidence to engage their family and community on health promotion, including HIV prevention research procedures, thus improving their self-esteem and communication skills. Training and partnering with clinical trial participants as peer educators is an effective and sustainable community-based approach for HIV prevention.

A Simple Risk Prediction Algorithm for HIV Transmission: Results from HIV Prevention Trials in KwaZulu Natal, South Africa (2002-2012).

We aimed to develop a HIV risk scoring algorithm for targeted screening among women in South Africa. We used data from five biomedical intervention trials (N = 8982 Cox regression models were used to create a risk prediction algorithm and it was internally and externally validated using standard statistical measures; 7-factors were identified as significant predictors of HIV infection: <25 years old, being single/not cohabiting, parity (<3), age at sexual debut (<16), 3+ sexual partners, using injectables and diagnosis with a sexually transmitted infection(s). A score of ≥25 (out of 50) was the optimum cut point with 83% (80%) sensitivity in the development (validation) dataset. Our tool can be used in designing future HIV prevention research and guiding recruitment strategies as well as in health care settings. Identifying, targeting and prioritising women at highest risk will have significant impact on preventing new HIV infections by scaling up testing and pre-exposure prophylaxis in conjunction with other HIV prevention modalities.

Baseline Predictors of High Adherence to a Coitally Dependent Microbicide Gel Based on an Objective Marker of Use: Findings from the Carraguard Phase 3 Trial.

A randomized, placebo-controlled, efficacy trial of Carraguard was unable to demonstrate a reduction in women's risk of HIV infection, which may have been due, in part, to low adherence (gel used in 42 % of vaginal sex acts, on average). A secondary analysis was undertaken to understand baseline factors associated with high adherence (gel used in ≥85 % of sex acts). Women who reported ≥1 vaginal sex act, returned ≥1 opened applicator, and had ≥1 conclusive post-enrollment HIV test (N = 5990) were included. Adherence was estimated as the ratio of average weekly applicator insertions (based on a dye stain assay indicating vaginal insertion)/average weekly sex acts (by self-report). Multivariate logistic regression modeling indicated that coital frequency, site, contraception, and partner age difference had a significant impact on adherence. Women reporting >1 and ≤2 vaginal sex acts per week, on average, were half as likely to be adherent as those reporting 1 vaginal sex act per week or less [adjusted odds ratio (AOR): 0.48; 95 % CI 0.38-0.61]; women from the Western Cape had one-third the odds of being adherent compared to women from KZN (AOR: 0.31; 95 % CI 0.23-0.41); compared to women using injectable contraception, women using any other or no method were more likely to be adherent (AOR: 1.30; 95 % CI 1.04-1.63); and women who had a larger age gap from their partners were more likely to be adherent (AOR: 1.03; 95 % CI 1.01-1.05; p = 0.001). Despite low adherence, overall, 13 % of participants achieved nearly perfect adherence, indicating a potential niche for a coitally dependent microbicide. More research is needed on the impact of sexual patterns and HIV risk perception on product acceptability and adherence to improve counseling in ongoing trials and when products are eventually introduced.

Characteristics Associated with HIV Drug Resistance Among Women Screening for an HIV Prevention Trial in KwaZulu-Natal, South Africa.

While the expansion of antiretroviral therapy (ART) in sub-Saharan Africa has reduced morbidity and mortality from HIV/AIDS, it has increased concern about drug resistance. The Microbicide Trials Network 009 study assessed the prevalence of drug-resistance mutations among women at clinical sites in Durban, South Africa who tested seropositive for HIV-1 at screening for the VOICE trial. The objective of this paper was to identify characteristics and behaviors associated with drug resistance. Factors found to be significantly associated with increased resistance were high perceived risk of getting HIV and prior participation in a microbicide trial, a likely proxy for familiarity with the health care system. Two factors were found to be significantly associated with reduced resistance: having a primary sex partner and testing negative for HIV in the past year. Other variables hypothesized to be important in identifying women with resistant virus, including partner or friend on ART who shared with the participant and being given antiretrovirals during pregnancy or labor, or the proxy variable-number of times given birth in a health facility-were not significantly associated. The small number of participants with resistant virus and the probable underreporting of sensitive behaviors likely affected our ability to construct a comprehensive profile of the type of HIV-positive women at greatest risk of developing resistance mutations.

To tell or not to tell: male partner engagement in a Phase 3 microbicide efficacy trial in South Africa.

Gender norms that privilege men's sexual power and pleasure, and distrust of condom use in intimate relationships, leave women vulnerable to HIV and other sexually transmitted infections. Vaginal microbicides allow women to exert a degree of control over their sexual health, through responsibility for product insertion as well as the possibility of covert use. In practice, however, the uptake of new HIV-prevention products is heavily influenced by partnership dynamics. This paper presents a secondary analysis of data from two qualitative sub-studies conducted during a Phase 3 microbicide efficacy trial in South Africa. Using transcripts from in-depth interviews and focus group discussions with 278 female trial participants and 27 male partners, we investigated the extent to which women disclosed microbicide use to their partners, and the level and types of male engagement with microbicide use. Most women chose to communicate with their partners about the trial, but the timing and content of associated discussions differed according to their motivation for disclosure. Men provided their partners with both moral and practical support, but reported a desire for greater involvement in decision-making surrounding microbicide uptake and use. The findings inform recommendations for constructive male participation in future trials and, ultimately, introduction of a marketed product.

A nationally representative survey of healthcare provider counselling and provision of the female condom in South Africa and Zimbabwe.

OBJECTIVES: Female condoms are the only female-initiated HIV and pregnancy prevention technology currently available. We examined female condom counselling and provision among providers in South Africa and Zimbabwe, high HIV-prevalence countries. DESIGN: A cross-sectional study using a nationally representative survey. SETTING: All facilities that provide family planning or HIV/sexually transmitted infection (STI) services. PARTICIPANTS: National probability sample of 1444 nurses and physicians who provide family planning or HIV/STI services. PRIMARY AND SECONDARY OUTCOME MEASURES: Female condom practices with different female patients, including adolescents, married women, women using hormonal contraception and by HIV status. Using multivariable logistic analysis, we measured variations in condom counselling by provider characteristics. RESULTS: Most providers reported offering female condoms (88%; 1239/1415), but perceived a need for novel female barrier methods for HIV/STI prevention (85%; 1191/1396). By patient type, providers reported less frequent female condom counselling of adolescents (55%; 775/1411), women using hormonal contraception (65%; 909/1409) and married women (66%; 931/1416), compared to unmarried (74%; 1043/1414) or HIV-positive women (82%; 1161/1415). Multivariable results showed providers in South Africa were less likely to counsel women on female condoms than in Zimbabwe (OR=0.48, 95% CI 0.35 to 0.68, p≤0.001). However, South African providers were more likely to counsel women on male condoms (OR=2.39, 95% CI 1.57 to 3.65, p≤0.001). Nurses counselled patients on female condoms more frequently than physicians (OR=5.41, 95% CI 3.26 to 8.98, p≤0.001). HIV training, family planning training, location (urban vs rural) and facility type (hospital vs clinic) were not associated with greater condom counselling. CONCLUSIONS: Female condoms were integrated into provider counselling and care, although providers reported a need for new female-initiated multipurpose prevention technologies, suggesting female condoms do not meet all patient/provider needs or are not adequately well known or accessible. Providers should be included in HIV training efforts to raise awareness of new and existing products, and encouraged to educate all women.

A qualitative study of obstacles to diaphragm and condom use in an HIV prevention trial in sub-Saharan Africa.

Consistent condom use and the substitution of condoms with potential HIV prevention methods of lower or unknown effectiveness are important concerns in the development of new prevention technologies. This qualitative study explored obstacles to consistent condom use with the diaphragm in MIRA, an HIV prevention trial in South Africa and Zimbabwe. We conducted 26 focus group discussions (FGDs) with 206 women and 7 FGDs and 10 in-depth interviews with 41 male partners of intervention-arm women. The belief that the diaphragm/gel prevented HIV, women's difficulties negotiating condom use, and men's unawareness that using the products together was recommended were obstacles to consistent condom use with the diaphragm/gel. Concerns about protection from HIV and pregnancy, recognition that the diaphragm was not yet proven to prevent HIV or sexually transmitted infections, and the trial context were facilitators. Understanding selective study product use in HIV prevention trials may inform improved adherence counseling and male involvement strategies.

User experiences and acceptability attributes of the diaphragm and lubricant gel in an HIV prevention trial in southern Africa.

Methods for Improving Reproductive Health in Africa (MIRA), a phase III HIV prevention trial, was conducted among 5039 Zimbabwean and South African women to test the Ortho All-Flex diaphragm and Replens(®) lubricant gel. Among the 2418 intervention group participants, 105 women who had completed the trial and 41 male partners participated in focus group discussions and in-depth interviews about the acceptability of the diaphragm and gel and their experiences using the study products. Women who participated in the qualitative study had exited the trial in the prior nine months, were HIV negative, and used the diaphragm and gel for 12-24 months. The comprehensive and flexible conceptual framework was applied to investigate the salient attributes for acceptability of the products as potential HIV prevention methods, and emerging themes for acceptability were framed within three categories of attributes (product, relationship, and sexual intercourse attributes). Both diaphragm and gel were found to be highly acceptable in the study group, and the gel was popular due to its effect of enhancing sexual pleasure. Some of the important product attributes influencing acceptability as reported by users were convenience, ease of use, dual use potential for contraception and disease prevention, and being female-initiated. It was also noted that some elements (such as sexual pleasure, couple communication, and the necessity of diaphragm negotiation) could be more important than others in terms of influencing product acceptability and use. Acceptability attributes reflective of the broader contextual environment (beliefs generated in the trial community suggesting preventive efficacy - preventive method optimism - and gendered norms favoring male superiority in sexual decision making) also emerged as important themes. The high level of acceptability of the diaphragm and gel among MIRA trial participants and their male partners is an indicator of the continued need for an effective female-initiated product.

Fostering community understanding of sufficient benefit and early stopping for a phase 2B HIV prevention clinical trial in Africa.

BACKGROUND: Most trials of interventions are designed to address the traditional null hypothesis of no benefit. VOICE, a phase 2B HIV prevention trial funded by NIH and conducted in Africa, is designed to assess if the intervention will prevent a substantial fraction of infections. Planned interim analysis may provide conclusive evidence against the traditional null hypothesis without establishing substantial benefit. At this interim point, the Data and Safety Monitoring Board would then face the dilemma of knowing the product has some positive effect, but perhaps not as great an effect as the protocol has declared necessary. PURPOSE: In March 2008, NIH program staff recommended that the VOICE protocol team discuss the stopping rules with stakeholders prior to initiating the protocol. The goals of the workshop were to inform community representatives about the potential ethical dilemma associated with stopping rules and engage in dialogue about these issues. We describe the resulting community consultation and summarize the outcomes. METHODS: A 2-day workshop was convened with the goal of having a clear and transparent consultation with the stakeholders around the question, 'Given emerging evidence that a product could prevent some infections, would the community support a decision to continue accruing to the trial?' Participants included research staff and community stakeholders. Lectures with visual aids, discussions, and exercises using interactive learning tasks were used, with a focus on statistics and interpreting data from trials, particularly interim data. RESULTS: Results of oral and written evaluations by participants were reviewed. The feedback was mostly positive, with some residual confusion regarding statistical concepts. However, discussions with attendees later revealed that not all felt prepared to engage fully in the workshop. LIMITATIONS: This was the presenters' first experience facilitating a formal discussion with an audience that had no advanced science, research, or mathematics training. Community representatives' concern regarding speaking for their communities without consulting them also created a challenge for the workshop. CONCLUSIONS: Open discussion around trial stopping rules requires that all discussants have an understanding of trial design concepts and feel a sense of empowerment to ask and answer questions. The VOICE CWG workshop was a first step toward the goal of open discussion regarding trial stopping rules and interim results for the study; however, ongoing education and dialogue must occur to ensure that all stakeholders fully participate in the process.

Assessing the accuracy of adherence and sexual behaviour data in the MDP301 vaginal microbicides trial using a mixed methods and triangulation model.

BACKGROUND: Accurate data on adherence and sexual behaviour are crucial in microbicide (and other HIV-related) research. In the absence of a "gold standard" the collection of such data relies largely on participant self-reporting. The Microbicides Development Programme has developed a mixed method/triangulation model for generating more accurate data on adherence and sexual behaviour. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected from a random subsample of 725 women using structured case record form (CRF) interviews, coital diaries (CD) and in-depth interviews (IDI). Returned used and unused gel applicators were counted and additional data collected through focus group discussions and ethnography. The model is described in detail in a companion paper [1]. When CRF, CD and IDI are compared there is some inconsistency with regard to reporting of sexual behaviour, gel or condom use in more than half. Inaccuracies are least prevalent in the IDI and most prevalent in the CRF, where participants tend to under-report frequency of sex and gel and condom use. Women reported more sex, gel and condom use than their partners. IDI data on adherence match the applicator-return data more closely than the CRF. The main reasons for inaccuracies are participants forgetting, interviewer error, desirability bias, problems with the definition and delineation of key concepts (e.g. "sex act"). Most inaccuracies were unintentional and could be rectified during data collection. CONCLUSIONS/SIGNIFICANCE: The CRF--the main source of self-report data on behaviour and adherence in many studies--was the least accurate with regard to measuring sexual behaviour, gel and condom use. This has important implications for the use of structured questionnaires for the collection of data on sexual behaviour and adherence. Integrating in-depth interviews and triangulation into clinical trials could increase the richness and accuracy of behavioural and adherence data.

A mixed methods and triangulation model for increasing the accuracy of adherence and sexual behaviour data: the Microbicides Development Programme.

BACKGROUND: The collection of accurate data on adherence and sexual behaviour is crucial in microbicide (and other HIV-related) research. In the absence of a "gold standard" the collection of such data relies largely on participant self-reporting. After reviewing available methods, this paper describes a mixed method/triangulation model for generating more accurate data on adherence and sexual behaviour in a multi-centre vaginal microbicide clinical trial. In a companion paper some of the results from this model are presented [1]. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected from a random subsample of 725 women (7.7% of the trial population) using structured interviews, coital diaries, in-depth interviews, counting returned gel applicators, focus group discussions, and ethnography. The core of the model was a customised, semi-structured in-depth interview. There were two levels of triangulation: first, discrepancies between data from the questionnaires, diaries, in-depth interviews and applicator returns were identified, discussed with participants and, to a large extent, resolved; second, results from individual participants were related to more general data emerging from the focus group discussions and ethnography. A democratic and equitable collaboration between clinical trialists and qualitative social scientists facilitated the success of the model, as did the preparatory studies preceding the trial. The process revealed some of the underlying assumptions and routinised practices in "clinical trial culture" that are potentially detrimental to the collection of accurate data, as well as some of the shortcomings of large qualitative studies, and pointed to some potential solutions. CONCLUSIONS/SIGNIFICANCE: The integration of qualitative social science and the use of mixed methods and triangulation in clinical trials are feasible, and can reveal (and resolve) inaccuracies in data on adherence and sensitive behaviours, as well as illuminating aspects of "trial culture" that may also affect data accuracy.

Experiences in conducting multiple community-based HIV prevention trials among women in KwaZulu-Natal, South Africa.

BACKGROUND: South Africa, with its scientific capacity, good infrastructure and high HIV incidence rates, is ideally positioned to conduct large-scale HIV prevention trials. The HIV Prevention Research Unit of the South African Medical Research Council conducted four phase III and one phase IIb trials of women-initiated HIV prevention options in KwaZulu-Natal between 2003 and 2009. A total of 7046 women participated, with HIV prevalence between 25% and 45% and HIV incidence ranging from 4.5-9.1% per year. Unfortunately none of the interventions tested had any impact on reducing the risk of HIV acquisition; however, extremely valuable experience was gained, lessons learned and capacity built, while the communities gained associated benefits. EXPERIENCE: Our experience in conducting these trials ranged from setting up community partnerships to developing clinical research sites and dissemination of trial results. Community engagement included setting up community-based research sites with approval from both political and traditional leaders, and developing community advisory groups to assist with the research process. Community-wide education on HIV/sexually transmitted infection prevention, treatment and care was provided to over 90,000 individuals. Myths and misconceptions were addressed through methods such as anonymous suggestion boxes in clinic waiting areas and intensive education and counselling. Attempts were made to involve male partners to foster support and facilitate recruitment of women. Peer educator programmes were initiated to provide ongoing education and also to facilitate recruitment of women to the trials. Recruitment strategies such as door-to-door recruitment and community group meetings were initiated. Over 90% of women enrolled were retained. Community benefits from the trial included education on HIV prevention, treatment and care and provision of ancillary care (such as Pap smears, reproductive health care and referral for chronic illnesses). Social benefits included training of home-based caregivers and sustainable ongoing HIV prevention education through peer educator programmes. CHALLENGES: Several challenges were encountered, including manipulation by participants of their eligibility criteria in order to enroll in the trial. Women attempted to co-enroll in multiple trials to benefit from financial reimbursements and individualised care. The trials became ethically challenging when participants refused to take up referrals for care due to stigma, denial of their HIV status and inadequate health infrastructure. Lack of disclosure of HIV status to partners and family members was particularly challenging. Some of the ethical dilemmas put to the test our responsibility as researchers and our obligation to provide health care to research participants. CONCLUSION: Conducting these five trials in a period of six years provided us with invaluable insights into trial implementation, community participation, recruitment and retention, provision of care and dissemination of trial results. The critical mass of scientists trained as clinical trialists will continue to address the relentless HIV epidemic in our setting and ensure our commitment to finding a biomedical HIV prevention option for women in the future.