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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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).
After confirmation of eligibility criteria, in-depth interviews were conducted where available RDL results were presented.
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).
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.
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.
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.
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.
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.
Abbreviations: CS, cellulose sulphate; DOH, Department of Health; DSMC, data safety and monitoring committee; HPRU, HIV Prevention Research Unit; MRC, Medical Research Council; PI, principal ...investigator In sub-Saharan Africa, almost 60% of HIV infections are among women 1, and the number of new HIV infections in women worldwide continues to escalate. Two have contraceptive properties, three (BufferGel, Carraguard, and PRO 2000) have displayed in vitro evidence of inhibition of other sexually transmitted infections, and all of them are coitally dependent--that is, they must be used just prior to sexual intercourse 5. ...recently there were five products in large-scale phase IIb/III trials 6: cellulose sulphate (Polydex Pharmaceuticals; http://www.polydex.com/) 7-11, PRO 2000 0.5% and 2% (Indevus Pharmaceuticals; http://www.indevus.com/) 12, Carraguard (Population Council; http://www.popcouncil.org/)13,14, and BufferGel (ReProtect; http://www.reprotect.com/) 15. The randomised controlled trial testing 6% cellulose sulphate against a placebo gel for effectiveness against vaginal transmission of HIV, sponsored by the reproductive health research organisation CONRAD (http://www.conrad.org/), was stopped following recommendations by the DSMC after preliminary data review of 1,333 enrolled women from five sites (South Africa, Uganda, Benin, and two sites in India) suggested that there were more HIV seroconversions in the cellulose sulphate arm compared to the placebo arm of the 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 six HOPE research sites in Lilongwe, Malawi; Durban (2 sites) and Johannesburg, South Africa; Kampala, Uganda; and Chitungwiza, Zimbabwe were randomly selected.
METHODS:Following confirmation of eligibility criteria, in-depth interviews were conducted where available RDL results were presented. ResultsMany 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 callenging 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, though 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.
Participant recruitment, retention and product adherence are necessary to measure the efficacy or effectiveness of an intervention in a clinical trial. As part of a Phase III HIV prevention trial in ...a rural area in Kwazulu-Natal, South Africa, a peer educator programme was initiated to aid in recruitment and retention of trial participants from the community. Enrolled trial participants who had completed at least 6 months of trial participation and who had honoured all of their scheduled trial visits within that period were approached to be peer educators. Following additional selection criteria, 24 participants were eligible to be trained as peer educators. Training topics included HIV/AIDS, sexually transmitted infections, nutrition, antiretrovirals, clinical trials, and methods of disseminating this information to the community. The role of peer educators was to bring interested women from their community to the trial site for comprehensive education and information about the trial and possibly trial participation. A total of 1879 women were educated by peer educators between July 2004 and December 2006. Of these, 553 women visited the trial site for further education and screening for participation in the trial. Peer educators provided continuous education and support to women enrolled in the trial which also promoted retention, ultimately contributing to the site's 94% retention rate. Recruitment and retention efforts of trial participants are likely to be enhanced by involving trial participants as peer educators. Such trial participants are in a better position to understand cultural dynamics and hence capable of engaging the community with appropriate HIV prevention and trial-related messaging.
Microbicides are most usually conceptualised within a disease prevention framework and studies usually define acceptability in terms of product characteristics, willingness to use and risk reduction. ...This starting point has led to assumptions about microbicides which, rather than being challenged by empirical studies, have tended to foreclose the data and subsequent conceptual models. Few studies take an emic ('insider') perspective or attempt to understand how microbicides fit into the broader context of women's and men's everyday lives. As part of the integrated social science component of the MDP301 Phase III microbicide trial, in-depth interviews were conducted with female trial participants in South Africa, Zambia, Tanzania and Uganda. Women's experiences of the gel challenge several assumptions that have commonly been reiterated about microbicides. Our analysis suggests that current definitions and conceptual frameworks do not adequately account for the range of meanings that women attribute to gel. Even within the context of a clinical trial, it is possible to obtain a richer, ethnographic and cross-cultural concept of acceptability based on women's practice and emic interpretations. We now need to move beyond limited notions of acceptability and consider how microbicides fit into a more holistic picture of women's and men's sexuality and sexual health.
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