Introduction

Women and girls are disproportionately affected by the HIV/AIDS epidemic, comprising about 57% of the estimated 25 million people living with HIV/AIDS in sub-Saharan Africa and approximately half of the global HIV/AIDS burden [1]. The impact of sexually transmitted infections other than HIV is also alarming, with the greatest burden faced by women in developing countries [2]. In addition to the burden of disease, the family planning needs of women across the globe far exceed adequate supply of, and access to, affordable contraceptive options [3]. Prevention methods that can be accessed and used effectively by women are urgently needed.

Intravaginal rings (IVRs) are emerging as potential devices for delivery of microbicides to protect women against HIV infection, and potentially ameliorate other sexual and reproductive health concerns. IVRs have a number of advantages over other prevention methods: they can be user-controlled, are potentially less detectable to male partners than topically applied peri-coital gel formulations, do not require daily or coitally-associated application [4], and can provide protection over long periods of time. Importantly, it may be possible to use IVRs to deliver more than one prevention active pharmaceutical ingredient (API), a concept known as multi-purpose technologies (MPT). This could include APIs to prevent other sexually transmitted infections, or contraceptive agents [5].

Several IVRs are currently on the market for contraceptive and hormone replacement purposes [6]. IVRs for delivery of microbicides to prevent vaginal HIV transmission are now in development and under evaluation. Phase I and II trials have demonstrated the safe and effective delivery of one anti-HIV microbicide in an IVR, and two efficacy studies are underway [7–9]. The completion and success of such a trial depends upon a number of factors, including maintaining product quality during large-scale production, minimizing the cost of materials and manufacturing, and designing an IVR that is feasible for long-term use [10–12].

Beyond feasibility, however, if a biomedical prevention strategy such as a microbicide is to be effective for HIV prevention, it must also be sufficiently acceptable to women, such that they are willing to use it consistently for extended periods of time. Phase III efficacy trials of HIV prevention microbicides delivered via vaginal gels have suffered from poor adherence to product use, which is likely, at least in part, affected by the user’s experience of the product during use [13–15]. The acceptability data from contraceptive and sexual health IVR technology have shown promising results, although acceptability has mainly been studied in the context of clinical trials [16–18] and clinical evaluation programs [19,20]. Within these studies, acceptability is generally assumed to correspond to continuation rate [16,18,21,22], or is assessed via questionnaire after several cycles of use [20,23,24]. Data from these trials suggest that most users find IVRs acceptable [25] despite reports of involuntary IVR expulsion [22,26] and interference with sexual intercourse [21,27,28].

Few in-depth (i.e., qualitative or mixed methods) studies have investigated the acceptability of IVRs among IVR-experienced or IVR-naïve women. Results from published studies highlight concerns related to IVR use, including the need for provider-facilitated education and counseling regarding insertion and removal, user concerns about feeling the IVR during intercourse, as well as during the course of the user’s daily activities, and the impact of IVRs on hygiene (particularly with long-term use [29–31]). The majority of acceptability data comes from women using IVRs in 28-day cycles (21 days of IVR use followed by 7 days without); however, a few studies have examined extended use regimens. Women using IVRs continuously for an extended period of time have found the devices generally acceptable, with most discontinuations due to menstrual irregularities secondary to IVR use for contraception [32–34]. In a study among Chilean women who used IVRs continuously for 3 to 14 months during breastfeeding instances of discontinuation were attributed to frequent expulsion, excessive vaginal discharge, interference with sex life, and user responsibility for insertion and removal (in comparison to physician insertion and removal, as with an IUD). Nonetheless, most women in the study reported an overall positive experience related to IVR use, and some who had discontinued IVR use expressed potential future interest in IVR use if their specific issues could be effectively addressed [31].

These preliminary explorations of acceptability are especially encouraging in light of research that suggests that an IVR releasing an anti-HIV microbicide is feasible [10] and potentially acceptable in areas where HIV is highly prevalent [30]. However, very little research has been conducted on IVR design preferences among women or their sex partners. Some female sex workers who handled a prototype IVR during a focus group study in urban Kenya expressed concerns that the IVR was too big (both overall ring circumference and cylinder diameter) and that the cylinder was too hard. Both male and female focus group participants in the study expressed concern about the device’s impact on male sexual pleasure [30]. While these data cannot assure prediction of rates of actual use, potential users’ first impressions of products can critically impact whether they try and/or continue with initial use and product adoption.

Early incorporation of user experiences and preferences in IVR design is critical, as parameters including size, material composition, and mechanical properties will likely directly affect acceptability and adherence [6], both initially and over time. Investigations of product properties are well-established in the food and cosmetic industries, but have not, until recently, been incorporated into the development of HIV prevention products or MPTs[35]. Studies are needed to systematically evaluate and measure users’ sensory perceptions and experiences of sexual health products to better understand the relationships between product properties and use patterns. Evaluation tools (i.e., Perceptibility Scales) used to objectively measure user sensory perceptions and experiences (USPE) of formulation and/or device characteristics and their performance during use, including sexual intercourse, are being developed to study properties of vaginal and rectal products (e.g., gels, films, and rings) that are most salient to users [36,37].

This pro-active, user-centered approach to prevention product design will facilitate success in future clinical trials and prevent the unnecessary use of resources on the development and clinical assessment of devices with little prospect of real-world acceptance. An IVR with an optimized user experience will be used by more women, more consistently, and as directed, therefore having the greatest possible impact on the HIV epidemic—or, in the case of MPTs, on a broader range of sexual and reproductive health conditions.

The current study explored the interaction of IVR materials, dimensionality (size/diameter), and biomechanical performance of four prototype IVRs among current and previous contraceptive ring users to more fully investigate the specific user sensory perceptions and experiences that might be relevant for the design of microbicide and multi-purpose technology IVRs. Our findings may be able to assist product developers in exploring the most salient factors that users consider in decision-making with respect to IVR use.

Methods

Participants

This formative qualitative work elicited the input of vaginal ring users, informed by their own product use experiences, to provide insight into the user sensory perceptions and experiences (USPE) most relevant for preclinical product design and iteration. The preclinical context imposes limitations on human subject research, minimizing sample sizes and activities to ensure subject safety. Participants were recruited from cities in the northeastern United States via community-based organizations, advertisements (print and online), and word of mouth. Recruitment materials invited vaginal ring users to attend a focus group to provide researchers with their opinions about how to design products women will want to use.

To be eligible for the study, women must have: 1) been 18–45 years old, 2) reported a regular menstrual cycle of 24–34 days, 3) reported vaginal sex with a man in the past 12 months, and 4) reported having used an intravaginal ring (IVR) within the last 12 months (i.e., all were recent or current contraceptive ring users). Women were ineligible if they were pregnant or breastfeeding to avoid any potential confounds with respect to motivations to use prevention products. Because participants would be manually manipulating prototype placebo rings in their hands during the focus group, women were also excluded for safety reasons if, upon inspection, they were observed to have signs of palmar or digital trauma, such as abrasions, cuts, or burns, as well as any dermatological conditions extending to their hands. All participants completed a brief sexual/reproductive health history and demographic survey prior to the start of the focus group discussion. Table 1 presents selected demographic characteristics for enrolled participants. IRB approval was granted by Lifespan/The Miriam Hospital Institutional Review Board (FWA00003538) and Western IRB (IRB00000533). All participants provided written informed consent.

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Table 1. Selected Demographic Characteristics of Sample.

https://doi.org/10.1371/journal.pone.0145642.t001

Results

Four semi-structured focus groups were conducted with a total of 21 women in the greater metropolitan areas of southeast New England. Data analyses suggest that five salient characteristics of the prototype intravaginal rings influenced women’s anticipated experiences in using IVRs for HIV prevention. These included the appearance of the surface of the cylinder material, the tactile sensations of the surface of the cylinder material, the perceived materials properties, the prototype rings’ dimensionality (i.e., cylinder diameter, outer diameter), and the interaction of these elements. Each was evaluated with respect to its impact on product use parameters. Women often used their experience with the contraceptive ring as a referent. Given the sample studied, the ring referenced was the NuvaRing^®, described as “a non-biodegradable, flexible, transparent, colorless to almost colorless,… [polymeric ring] with an outer diameter of 54 mm and a cross-sectional [cylinder] diameter of 4 mm” [39]. Overall, the majority of participants noted that Rings A and B were most like the intravaginal ring with respect to material and dimensional properties. Relevant quotes are provided in Table 2.

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Table 2. Summary Participant-derived Characteristics, Primary Attributions, and Selected Illustrative Participant Quotes by Ring Characteristic.

https://doi.org/10.1371/journal.pone.0145642.t002

The Interaction of Materials and Dimensionality

Participant evaluations of material properties often interacted with other properties and characteristics in their discussions of salient ring use parameters. In particular, material properties interacted with perceptions of cylinder diameter, as well as overall ring diameter, to create anticipations regarding ring pliability and flexibility, with important considerations for the insertion experience.

To return to the discussion of size, comfort seemed the primary concern when efficacy was anticipated as equivalent across prototype options. Participants in at least two groups agreed that developers could make the overall diameter of the ring bigger if the cylinder diameter was small and the material was soft. Indeed, material properties interacted with cylinder diameter with respect to perceptions of flexibility. Thus, a smaller cylinder diameter using the softer of the materials made for a more flexible ring. A flexible ring was seen as one that would be pliable and easier to squeeze, making the insertion experience tolerable, if not inconsequential. A flexible ring was also seen as more comfortable, conforming to the body and staying in place better than a rigid ring. Flexibility was a particularly important characteristic for those women who preferred to insert their contraceptive ring in a folded-over figure-8 shape (see Fig 1).

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Fig 1. Variations in participant folding/squeezing techniques for IVR insertion.

Panel A: standard squeezing of IVR involving squeezing the ring between the thumb and middle finger and using the index finger to guide, then push the ring further into the vagina. Panel B: squeezing of IVR using both the index and middle finger on one side and the thumb on the opposite side, for initial insertion; then using fingers to push the ring into place in the vagina. Panel C: the “figure-8” folding method involving squeezing the ring in the middle, twisting it at the center to make a figure-8, then folding it over, and holding the ends together for insertion.

https://doi.org/10.1371/journal.pone.0145642.g001

Flexibility allowed the fold to open and the twist to come undone, something some participants said they could feel happening in the vagina on insertion. The harder material, especially when combined with a larger cylinder diameter, gave the impression of a ring that would be difficult to squeeze for insertion, and would result in an array of ‘insertion hold’ contortions by the participants. Some participants even experienced tiring and tightness of their fingers, in attempting to hold the ring in the squeezed position during the discussion. Further, they felt the more rigid rings would not conform to their vaginal anatomy, that they would be aware of it physically as an object in their vagina, and that it would feel unnatural, especially during sex.

In addition to issues with the force it would take to squeeze and/or hold the ring in a given position for insertion (“squeeze force”), participants also discussed recoil, labeled as “spring back” or “sproing.” These terms referred to the ring’s return to its seated shape and ‘time-to-seat’ within the vagina once they let it go during insertion. Women had particular notions about whether the ring returned to its circular shape, or took on a more oval shape, once in the vagina, as well as how quickly the ring would return to that shape once they release their squeeze. Some women reported previous experiences where they had felt their contraceptive ring “spring” back into place after insertion. A quick, forceful movement was not preferred by the participants, but neither was a slow movement with no detectable force. For many participants, a ring that returned to its original circular shape was perceived as one that would stay in place better. A ring that sprang back relatively quickly but not forcefully would be more appealing, as they would have the sensation that it settled into place, and would consequently feel protected. There was concern by some participants that a ring that sprang back too slowly would not settle well into a comfortable position and might slide out of the vagina if it did not return to its original circular shape.

Discussion

The main goal of this investigation was to assist IVR prevention product developers in identifying the most salient user-identified product characteristics to be considered in both product design and adherence support in clinical trials and eventual real-world use. Four prototype IVRs were developed for this formative perceptibility and user experience study. We explored the relationship between product materials, dimensionality, and their interactions (e.g., pliability, flexibility) in an effort to identify and understand how these properties might impact potential users’ sensory perceptions and appraisals of use. Enrolling current and previous ring users allowed participants to use their experiences with IVRs as a point of reference, and gave them an opportunity to describe the most salient aspects of IVR use and what the prototype rings might feel like in the vagina. The prototype placebo IVRs used in this study were not under investigation in any previous, ongoing, or planned clinical trials, nor were these prototypes rings used intravaginally at any point by our study participants. The four prototypes were produced, not to find an ideal or preferred product to advance to specific clinical trials, but to qualitatively explore a range of IVR parameters and the user sensory perceptions and experiences those properties might elicit. Therefore, our findings focus not on determining a single preferred product, but on the most important product characteristics and/or properties for product developers to consider when designing and evaluating candidate IVRs, and to begin to understand concerns about expectations of use that may need to be addressed with provider and patient education.

Pliability (or flexibility) was discussed at length in each of the focus groups, and was generally considered to be the most important IVR property. Pliability, as described by the participants, seemed to be a composite characteristic influenced by materials and dimensionality, had implications for ring insertion and vaginal placement, comfort during daily use, and comfort for both partners during vaginal intercourse. Within the context of these participants’ typical IVR use (i.e., hormonal contraception restricted to 21-day use followed by 7 days for menses), most, though not all, participants stated that the prototype IVRs varied in their flexibility and stiffness, and were at least somewhat less flexible, and more stiff, than the contraceptive rings they had used; this was generally regarded as a negative characteristic of the prototypes. More pliable IVRs were believed to be easier to hold on to for insertion, easier to place in the vagina, and less intrusive for daily wear, as well as for comfort and unobtrusiveness during sexual intercourse. As noted above, however, when the discussion shifted to HIV prevention, product properties such as pliability and dimensionality (see below) became more negotiable, as participants considered whether more drug volume and/or greater durability of material over longer periods of time might be required.

Perceived product efficacy is another concept that was of particular importance for women and may be directly related to some product properties and purposes. Our previous work has demonstrated that women’s willingness to use HIV prevention products may depend on the user’s perceived product efficacy [40]. In the current study, participants related the perceived porousness of the IVR to its ability to effectively deliver active drugs to the vaginal environment. Regardless of whether a shiny versus matte finish is, in fact, related to the porosity of the ring, and regardless of whether that porosity corresponds to appropriate drug delivery, women’s understandings may influence their willingness to initiate and maintain product use [41]. Similarly, ring size, whether in cylinder diameter or overall ring diameter, also had implications for perceived product efficacy: participants believed that the greater the ring’s capacity to hold a drug, the more likely it would be to work, and/or work for longer periods of time in the case of long-term resident products. These characteristics are under the direct control of product developers, and such information can be used to either alter product prototypes early in the design and evaluation process, or produce educational material to preemptively address user concerns.

Hygiene and other biological concerns may represent other critical components of designing effective IVRs. Some women noted that they had removed the contraceptive ring and rinsed it during their normal showering/bathing routines. This is in line with research from the International Partnership for Microbicides indicating that between 4% and 18% of women reporting removing or expulsing the ring with many of them reporting removing the ring during menses or for periodic cleaning [42]. While women in our study had experience only with 21-day on/7-day off cycle IVRs, it may be especially important to consider hygiene concerns for HIV/STI prevention rings and MPTs as ring residency in the body advances beyond the traditional 28-day cycle. It was also noted during the focus group discussions that sustained release IVRs might be acceptable for STI prevention, including HIV, but this was sometimes countered by those participants who preferred regular menstrual cycle bleeding, as well as those concerned with having synthetic (e.g., plastic) materials in their bodies for long periods of time[41].

The impact of IVRs on the sexual experience, and the potential compensatory behaviors of IVR users, may be another important aspect to consider in IVR design. Some study participants reported removing the contraceptive ring in the context of sexual intercourse. While it is possible to remove the hormonal contraceptive ring for a few hours and not increase one’s risk for conception, depending on the specific active pharmaceutical in an anti-HIV/STI or multipurpose prevention ring, removing the ring from the vagina for extended periods of time may have a significant and deleterious impact on product efficacy. Thus perceptibility and user experiences will be important to consider in drug delivery and device design, to allow for the least likelihood that users will feel the need to remove the ring for any reason, whether sex or hygiene.

The IVR prototypes evaluated in this formative perceptibility and user experience study were limited to four prototypes that varied on two key product characteristics: cylinder diameter and materials. Other properties such as overall ring diameter were not systematically varied in this study, although emerged spontaneously in the discussion of potential increases in cylinder diameter and/or long-term residency. As intravaginal ring design work continues, other materials, properties and dimensionalities should be considered with respect to user perceptions and experiences. Additionally, these findings represent the opinions of contraceptive IVR users in the northeastern United States. Our participants were, in general, well educated, unmarried, nulliparous, Caucasian women of reproductive age. Future MPT studies will be necessary among women in other geographical regions and cultures, to understand the range of sensory perceptions and experiences of IVRs and to represent a wider range of parity, BMI, education, income and ethnicity than the participants recruited for the current study. Additionally, future work should also address the needs of adolescent girls younger than 18 and menopausal women older than 45, as both groups can be at risk of HIV and STI infection, but will likely have differing needs based on their reproductive biology and needs. We note that there are no IVR studies to date showing the predictive value of in mano (i.e., in the hand) evaluation to intravaginal perceptions, willingness to use, or sustained consistent use. Although the participants did not evaluate the prototype IVRs intravaginally in the context of this study, this preclinical study was designed to enroll women with previous experience with a contraceptive ring, so that that experience could inform both their comparisons with respect to sensory data, and their opinions regarding those comparisons. This is in contrast to potential concerns regarding generalizability of the sample: the findings might only apply to women willing to insert and use a 28-day hormonal IVR. While using an IVR-experienced sample sets the possibility of familiarity bias, the goal of the study was to identify and describe the range of properties that could be experienced by actual IVR users, and hence the range of properties product developers should consider in a user-centered approach to IVR design.

Given the lack of previous research in intravaginal ring perceptibility, we remain confident that these data and insights into user perspectives are of significant importance to the field’s drug delivery system design efforts. For instance, conventional acceptability studies of IVRs—conducted in the context of clinical trials—report high user acceptability in spite of ring expulsions and interference during sex. Qualitative studies such as this one advance understanding of user experiences by elucidating users’ compensatory behaviors, such as removing rings prior to sexual intercourse to maximize comfort, or rinsing rings due to hygiene concerns. With this information in mind, developers can design a ring that either minimally interferes with sexual intercourse, or that will remain protective against HIV/STI infection even if the user removes the ring for (at least) the duration of a sexual encounter. Similarly, preclinical studies should evaluate drug bioavailability and delivery in contexts where regular rinsing for hygiene purposes is anticipated. Further, it will be important to move forward in developing validated measures of user sensory perceptions and experiences of intravaginal rings and other drug delivery systems to systematically assess the impact of users’ sensory perceptions of product properties, with the goal of developing effective biomedical HIV/STI prevention products and multipurpose prevention technologies.

The context and range of discussions in this study, beyond those unique to specific physical and mechanical ring characteristics, are worth consideration in the larger scope of intravaginal ring development. The potential for covert use and the potential to maintain or enhance sexual pleasure remain critical considerations as the field continues to strive for the development of highly effective prevention technologies. Both are multifactorial constructs that complicate interpretations of data in conventional microbicide acceptability studies occurring within the context of late-stage clinical trials. Importantly, each is inextricably related to additional psychosocial determinants of use beyond the scope of preclinical product design. In the context of preclinical perceptibility evaluation such as this study, multifactorial constructs such as covert use and sexual pleasure are, in the case of intravaginal rings, importantly governed by materials and mechanical properties. Overall, the need to balance product materials, dimensions and use parameters to optimize drug delivery and optimize the user experience appears as important in intravaginal ring design as we find it to be in the design of topical formulations such as gels, films and other semi-solid topical drug delivery systems. We believe that by attending to these findings, product developers can leverage good user-centered product design strategy to optimize adherence to use.

Acknowledgments

The authors are grateful to the women who participated in the study and the community-based organizations that collaborated to facilitate recruitment efforts. This research team has documented the meaning users make of their experiences with vaginal products. Some of that work used a small subset of the data presented here, along with data on vaginal gel formulations, as examples of the meaning-making process. This manuscript presents our full IVR product evaluation results and illustrates the importance of materials, dimensionality, and their interactions, to support user-centered product design. The content is solely the responsibility of the authors and does not necessarily represent the official views of the study’s funders.