“Set it and forget it”: Women’s perceptions and opinions of long-acting topical vaginal gels

Abstract

Women’s initial understandings and anticipated acceptability of long-acting vaginal gels as potential anti-HIV microbicides was investigated by exploring the perceptibility variables associated with prototype formulations. Four focus groups with 29 women, aged 18–45, were conducted to consider gel prototypes with varied physicochemical and rheological properties. Participants responded favorably to the concept of long-acting vaginal gels as microbicides. Distinctions in understandings and stated needs regarding product dosing, characteristics, and effectiveness offer valuable insights into product design. Long-acting vaginal gels capable of protecting against HIV/STIs will be a viable option among potential users, with dosing frequency being an important factor in willingness to use.

Introduction

The HIV/AIDS epidemic continues to be a global public health priority, with 34 million individuals living with HIV infection worldwide as of 2011, including 16.7 million women [1]. Many technologies and strategies have been investigated to address the prevention of HIV transmission. Notably, oral pre-exposure prophylaxis or PrEP with antiretroviral agents has been shown to be effective in some populations [2–4]. In addition, topical vaginal and rectal microbicides are substances that may prevent the transmission of HIV and/or other sexually transmitted infections (STIs) [5]. The course of microbicide development has been challenged by several disappointing efficacy trials. To date, one trial has provided evidence of the prevention potential of vaginal microbicides, but has yet to be confirmed. In that trial, 1% tenofovir gel reduced HIV infections among trial participants by 39% overall [6]. Product developers continue to design and evaluate new drug delivery systems (DDS), both topical formulations and devices, for HIV prevention [7, 8]. Among those in clinical trials are reformulated tenofovir gel, fast-dissolve vaginal tablets, and intravaginal rings (IVRs) [9]. Those in preclinical development include IVRs with alternative active pharmaceutical ingredients (APIs), quick-dissolving films, suppositories, DDSs that capitalize on nanotechnology, and drug-eluting fibers [10–19].

Throughout the development of microbicides, researchers and advocates have emphasized the need to investigate microbicide “acceptability” and adherence. If a product is acceptable to users within the context of their daily lives and sexual experiences, it will presumably be used more effectively and with greater adherence. Evidence for the importance of the link between anti-HIV efficacy and correct and consistent use (i.e., adherence) was seen in the clinical evaluation of 1% tenofovir gel: women who used the product for more than 80% of sex acts experienced a greater reduction in the rate of HIV transmission (54%) than those who did not (28–38% in low and intermediate adherers, respectively) [6].

Formative studies of microbicide acceptability have assessed and defined acceptability differently [20–22]. Some have evaluated acceptability by providing participants descriptions of hypothetical products; participants would then be asked about the likelihood that they would use such products. Other investigators have asked participants to try over-the-counter or placebo vaginal products and assessed opinions and predictions as to whether they could be used as a microbicide [23, 24]. Despite the important contributions prior formative research studies have made to our current understanding of microbicide acceptability, they have been limited in terms of predicting the likelihood of actual use (i.e., adherence) within clinical trials. In some trials where acceptability was found to be high, adherence was not as high as would have been predicted based on reports of acceptability alone [20, 25, 26].

To better understand the factors that impact what is presumed to be the multi-factorial nature of "acceptability," we began to study the sensory perceptions and experiences elicited by vaginal product formulation properties. In Project LINK, Morrow et al. [27] developed and psychometrically evaluated a series of "perceptibility" scales that capture specific and distinct user sensory perceptions and experiences elicited by the biophysical properties (e.g., measured rheological properties such as viscosity and its dependence on shear rate) and intravaginal spreading(estimated from computational models) of semi-solid formulations. In the case of vaginal microbicide development, semi-solids are topically applied formulations (e.g., gels) that are flexible and deform when in the hands or otherwise observed out of the body. They are subject to dilution after insertion into the vaginal canal and contact with ambient vaginal fluids. Dilution causes changes in the rheology and other biophysical properties of the material (e.g., viscosity is lower), putatively changing the sensations elicited by the product and, potentially, how the product is perceived by the user. Project LINK established that users could clearly distinguish one formulation from another and, further, that their sensations and experiences with various formulations impacted their choice of formulation for future use. We posit that, by using preclinical formulation perceptibility data to guide the design of microbicide formulations, the user experience can be optimized, potentially leading to higher rates of acceptability and use.

Thus, in contrast to human clinical trials that capture a candidate microbicide’s conventional acceptability data such as the users’ like or dislike of the product’s color, smell, and propensity for leakage or covert use, we assess the users’ willingness to use the product based on the characteristics of that formulation, including, but not limited to its biophysical properties and rheological performance parameters, the application process, and the presumed duration of effectiveness [22].

Inherent to the discussion of willingness to use microbicide products is the need to adhere to the anticipated dosing regimen. This includes whether the product is designed to be coitally-associated (i.e., required to be applied coincident with intercourse), or coitally-independent (i.e., required to be applied at specific intervals without regard for sexual activity: e.g., designed for daily use). The CAPRISA 004 dosing regimen, designated “BAT-24,” was a coitally-associated regimen, with a first dose (4 mL) of 1% tenofovir gel to be administered within 12 hours of the start of intercourse, and a second dose (4 mL) to be administered within 12 hours after intercourse. The current phase IIIFACTS 001 study of the same product requires the same regimen. The dosing regimen for the VOICE (MTN 003) study was a coitally-independent daily dose (4 mL). Inherent in the dosing regimen of various DDSs are other requirements, including the timing of the dose. For coitally-associated DDSs, as with BAT-24, a 12-hour timeframe was prescribed, but the timing of dosing could also include such prescriptions as the need to wait for 10–20 minutes while a film or tablet dissolves prior to intercourse, or the need to leave a diaphragm or other barrier device in the vagina for several hours post-coitus. For coitally-independent DDSs, timing requirements are more akin to those prescribed by oral contraceptive methods (the requirement to administer the drug at/around the same time every day). These requirements alone can impact a potential user’s willingness and ability to adhere to administration instructions, but they can also impact the overall user experience with respect to sensory perceptions and experiences of formulation or device properties. For example, in CAPRISA 004 adherence was measured through monthly self-reports and counts of used and unused gel applicators returned by participants at follow-up visits. In addition, motivational interviewing was used to support and increase adherence to gel use. On average, adherence was high (defined as a median adherence score of >80%) in this trial with 72.2% of reported sex acts by participants being covered by two doses of tenofovir gel [6].

The current study was designed to investigate women’s opinions regarding a more nuanced aspect of dosing regimen: a longer duration of effect in a product administered less frequently (i.e., long-acting). In this scenario, a dose could, for instance, be administered every 7^th day, with prevention efficacy lasting the duration of the inter-dosing latency. We examined women's experiences of the biophysical characteristics of different vaginal gel formulations to inform early-stage product development and to have hypothetical discussions of a "long-acting" gel using proxy products as a way to focus on specific biophysical characteristics. The research question considered whether these long-acting gels that are not coitally-associated would require a different understanding of the interplay between sexual and prevention behaviors. This has implications both for anti-HIV microbicide development, and for the development of multipurpose prevention technologies (MPT). MPTs are single formulations or devices currently in development that prevent two or more sexual and reproductive health risks: HIV and other sexually transmitted infections (e.g., gonorrhea, Chlamydia, or human papillomavirus, and/or unintended pregnancy). As will be seen, what emerged from the focus group discussions was the consideration of the similarities and differences between “long-acting” and “long-term residence” (or sustained release) gels.

Methods

Study design and protocol

Participants were recruited from two cities located in the northeastern United States through community-based organizations, advertisements, and word-of-mouth. A brief pre-screening questionnaire was administered verbally by phone to assess study eligibility criteria (i.e., 18 to 45 years old, regular menstrual cycle, vaginal sex with a man in the past 12 months, prior or current use of a gel or lubricant in the past 12 months, and ability to provide informed consent). Following consent, participants completed a brief written demographic and sexual and reproductive health history questionnaire. Women washed their hands with unscented soap and dried them with lint-free disposable towels prior to each product demonstration. Focus groups were co-facilitated by doctoral-level investigators experienced in qualitative methods and microbicide acceptability research. Participants were compensated $30 for their participation in the focus group and reimbursed $10 for transportation and/or child care costs. This study was approved by the appropriate institutional review boards.

Study products

In each focus group, participants discussed current and previous experiences with vaginal gels/lubricants. Following this discussion, three over-the-counter vaginal lubricants were placed in the center of the participants’ palm of her non-dominant hand using a pre-filled applicator, one at a time: K-Y^® Jelly, Replens^®, and Pre-Seed^®. The formulations were chosen to represent a range of physicochemical and rheological properties and performance characteristics thought to impact user sensory perceptions and experiences, as well as delivery of a drug to the vaginal vault [Refer to Table 1]. The order of presentation was randomized for each group.

Table 1.

Study vaginal gel characteristics

Gel	Volume expressed in mano	Viscosity at 1/s (Pa-s)a	Viscosity at 100/s (Pa-s)b	Residual Stress (Pa)	Ingredients
Pre-Seed (undiluted)	3.5 mL	2.512	N/A	0	purified water; hydroxyethylcellulose; pluronic 127; sodium chloride; arabinogalactan; sodium phosphate; carbopol 934; methylparaben; sodium hydroxide; potassium phosphate
KY Jelly (undiluted)	3.5 mL	42.61	2.132	0	purified water; glycerin; hydroxyethylcellulose; chlorhexidine gluconate; gluconolactone; methylparaben; sodium hydroxide
Replens (undiluted)	3.5 mL	97.71	1.914	57	purified water; glycerin; mineral oil; polycarbophil; carbomer homopolymer type B; hydrogenated palm oil glyceride; sorbic acid; methylparaben; sodium hydroxide

Note: The three over-the-counter topical vaginal gel formulations used were chosen to represent a range of physicochemical and rheological properties and performance characteristics considered reasonable for microbicide development. N/A = instrument over range before reaching this shear rate. Pa-s indicates unit of measure of viscosity, corresponding to the colloquial notion of “thickness.”

^aViscosity at 1 sec⁻¹: characteristic of gel flow along the vaginal canal

^bViscosity at 100 sec⁻¹: characteristic of coital activity

Participants experienced each product in their hands according to the facilitator's directions from an “in mano” manipulation script. Each product demonstration and discussion lasted 15 to 30 minutes. Following the in mano experience, participants rinsed their hands to determine how the product would respond to water, and then used unscented soap to experience the products’ response to detergent. The remaining time was spent discussing product behavior and characteristics and comparing demonstration products to each other. Participants were also shown a high-viscosity clear gel in a large sealed clear glass tube, and informed about potential long-acting products and how they might differ in their physicochemical and rheological properties from those they had experienced during the earlier portion of the discussion. The high-viscosity clear gel was not placed in participants hands.

Data collection and analysis

A semi-structured focus group agenda was developed from an extensive review of the microbicide formulation and acceptability literature. The agenda was also informed by the investigators’ prior experience with acceptability studies, and user sensory perception and experience studies (i.e., preclinical perceptibility studies), as well as the products’ hypothesized correspondence with biophysical properties and functionality. Participants were asked to consider the feel and behavior of the products, and: (a) discuss their anticipations of the application/insertion process; (b) describe if, when, and under what conditions the formulation might leak from the vagina; (c) explain anticipated awareness of the formulations, including the perception of moisture or wetness; (d) consider the formulation’s potential effects on the experience of intercourse (e.g., lubricating or desiccating properties, perceptions of altered sensations during intercourse, potential effects on sexual pleasure and/or comfort); (e) consider whether the formulations might be used covertly, and (f) discuss perceptions of how a gel would feel (or the physical sensations and meaning of having products) in their bodies that may change form and/or reside there for some period of time. Throughout the discussion, participants were asked to consider and assess both positive and negative aspects of product use. It is in this context that the contrasts in user perceptions between long-acting and long-term residence products became apparent.

Focus groups were audio recorded and transcribed verbatim. Transcripts were reviewed for accuracy, participant identifiers were removed, and transcription errors were corrected. A qualitative data coding structure was used to identify relevant themes and content. Emergent themes were added to the coding structure as they were identified. Each transcript was coded by two independent coders, who then compared coded transcripts to resolve any discrepancies prior to final codes being entered into NVivo 9, a software program used to facilitate qualitative data management and analysis [28]. Entered codes were reviewed in aggregate for thematic analysis. In addition, a framework matrix was created to synthesize the responses to specific product characteristics and to capture the range and representativeness of those responses.

Results

Twenty-nine (29) women participated in four (4) focus groups. Demographic characteristics of the sample are summarized in Table 2. Of note, 38% were non-Caucasian/White, and over one-quarter reported income below $15,000 annually. The majority of the participants had used vaginal medications and vaginal products other than lubricants, indicating a degree of familiarity in inserting and sensing products in their vaginas. All participants reported recent or current use of a variety of lubricants in different forms including gel, cream, liquid, and suppository.

Table 2.

Demographic characteristics of sample (N = 29; k = 4^a)

	Mean	SD
Age	31.5	7.1
	N	%
Ethnicity
Hispanic/Latina	2	6.9%
Race
Black/African American	2	6.9%
Caucasian/White	18	62.1%
Asian	2	6.9%
Multiracial or other	7	24.1%
Education
Less than high school	1	3.5%
High school	3	10.3%
Beyond high school	25	86.2%
Current Marital Status
Never been married	15	51.7%
Married	10	34.5%
Separated	1	3.5%
Divorced	3	10.3%
Household Income (annual)
<$15,000	8	27.6%
$15,000–$35,999	10	34.5%
>$36,000	10	34.5%
Not reported	1	3.4%
Sexual History
Oral sex in past 12 months	23	79.3%
Anal sex in past 12 months	6	20.7%
Vaginal Product History
Vaginal medication	23	79.3%
Vaginal douche	12	41.4%
Spermicides	9	31.0%
Desiccants	2	6.9%
Intravaginal rings	7	24.1%
Number of Vaginal Deliveries
0	23	79.3%
1	3	10.3%
2 or more	3	10.3%

^anumber of focus groups

Initial Impressions of Long-Acting Vaginal Gel

The majority of women responded favorably to the concept of a long-acting vaginal gel as a microbicide. Most participants also showed interest in the idea of inserting a vaginal gel up to 48 hours prior to coitus. This was reflected in statements made by participants who noted that it could be an effective way for women to protect themselves since some sexual activities may be unplanned. Similarly, participants surmised that a long-acting gel would allow a woman to insert the product into her vagina and forget about its presence but still be protected against HIV and other STIs. One participant explained, “Kind of like, ‘set it and forget it…’ like a crock pot. You put it in there and you kind of forget about it. And that way - because I feel like… if it’s something that you insert and deposit it…you know that they are in there.” A different participant concurred, “Like when you have sex, you never know when it’s going to happen…and I think that that seems like a way that you could put it in and kind of forget that it’s even there.”

Perceptions of Long-Acting Vaginal Gel Characteristics

The ideal vaginal gel characteristics identified by these women included easy application, lack of odor, and discreet in terms of color and consistency (most preferred the product to be clear; a thick, white product, similar to a yeast infection medication, was not preferred). Ideal characteristics varied, however, by product indication: participants tended to prefer a thicker, adherent consistency if intended for HIV/STI prevention, and a thinner consistency for lubrication needs. They had positive opinions regarding a proposed long-lasting product that was comfortable and not messy (to avoid leakage), and was adherent to the vaginal epithelium. This preference for adhesive properties was endorsed by those who felt that they would feel more confident in a product’s ability to provide protection if they believed it was able to provide a physical barrier to HIV/STIs (i.e., by adhering to the vaginal tissue).

Long-Acting Vaginal Gel for HIV/STI Prevention and Sexual Lubrication Needs

Participants’ discussions revealed a distinction between the concept of a long-acting vaginal gel acceptable for protection against STIs/HIV and their general sexual lubrication needs. This opinion appeared to be influenced by participants’ views of how the products would feel and behave once applied. For HIV/STI prevention, several women discussed their desire for a long-acting vaginal gel that would be thick and stay in place to serve as a protective barrier against diseases. For lubrication needs, however, women expressed interest in a vaginal gel that was thinner (less viscous) and would spread quickly to cover (or coat) the inside of the vagina. One woman stated that, “Protecting from HIV and lubricants…I’m thinking of it in two different worlds.” Another participant explained further that, “If the function is that I am wanting a long-action gel that’s gonna then help me keep safe from HIV, then yes, I would use it [a gel with a thicker consistency]. If the function is this is what I’m gonna use during sex to make sex either easier or more fun, then probably not so much.”

Ideal Consistency of Long-Acting Vaginal Gel for HIV/STI Prevention

Participants stressed the importance of a long-acting vaginal gel’s ability to adhere to the vaginal epithelial tissue to increase protection against the transmission of STIs/HIV. Considering the ability of a gel to provide a physical barrier for protection against HIV/STI, a few women indicated that the ideal consistency of the long-acting vaginal gel depended on whether it was meant to stay in place, or if it was meant to be removed or dispelled from their body immediately after intercourse. For most women, the thickness of the gel seemed to signal that the product would remain in their vaginas to reduce the risk of acquiring an infection (e.g., STIs/HIV). When considering less viscous products as possible long-acting gels, women raised concerns regarding the potential for leakage and rheological changes over time, which was interpreted by them as a reduction in the effectiveness of the product as a protective barrier. One participant expressed her concern regarding potential leakage as, “[you] don’t want something goopy that is potentially going to essentially leak out, and then you end up with stainage or whatnot, especially for that amount of hours.” Another participant added that, “I want it to be thick. I want it to stay in place…is it going to stay up there and do its job, or is it going to be coming out?”

Changes in Long-Acting Vaginal Gel Characteristics over Time

Most women responded positively to the concept of a long-acting vaginal gel that was initially thin (less viscous) and became thicker (more viscous) within a short time-frame. However, some of the participants expressed concerns about potential leakage when the gel was in the thinner (less viscous) state. One woman articulated her leakage concerns as being related to potential temperature changes within her body noting that, “I’d be afraid that it would get warmer and just kind of like drizzle out.” When presented with the concept of a hypothetical product that could be inserted and remain in their vaginas until, for instance, semen is introduced and the active ingredient is released, most participants were amenable to the idea. They were also open to the idea of gels that they and their partner(s) would be unaware of; that might change with respect to properties and, therefore, “feel” given dilution or other changes in environmental conditions as a function of sexual intercourse; and that would serve as a protective barrier against HIV/STIs. One participant said, “So I kind of like the idea of something that you can insert into your body that’s gonna activate itself or whatever, and provide a barrier for microbes and disease and stuff like that. But you’re not necessarily aware of it. You can’t feel it coming back out.”

Application of Long-Acting Vaginal Gel

Some participants found plausible the concept of a gel that could confer protection against sexual risk for multiple days, when a dosing regimen was unassociated with coitus. One participant suggested, “If you have something where it’s long-lasting, …and you do it once a week, say on Sunday…it will cover you all the way until the next Sunday.” However, when asked if women would use a long-acting vaginal gel that could be applied daily (i.e., not coitally associated, long-acting) versus one that could be applied prior to coitus but continue to last beyond coitus (peri-coital with long duration of effect), most of the women reported that they would prefer to apply a gel on the day that they believed they would need it for sexual intercourse. One participant noted, “So if it were me, I would probably just use it when I’m going to have sex.” A different participant concurred, “I think it’s the day that you think you’re going to need it.” Reasons for responding unfavorably to long-term daily use (i.e., not coitally associated) included the anticipated high cost and inconvenience associated with using such a product every day, as well as the perception that the product would be invasive since it would be a foreign substance in their bodies.

Discussion

Coitally-independent topical microbicide products have primarily been conceived as products to be applied once daily. However, some research suggests that the requirement of daily dosing may contribute to poor adherence [29, 30]. We present data that elucidate women’s opinions regarding potential microbicide products that could be applied less frequently than once a day, and would be able to confer protection over an extended period of time (e.g., several days). Women were presented with a range of vaginal products, similar to over-the-counter lubricants or vaginal moisturizers, and asked to consider their use as products that could provide protection from HIV/STIs for several days. Women were then asked how long they would want a single application of the product to provide protection. This line of questioning exposed differences in the ways in which women understood how a product would provide protection and demonstrated the need to reconsider, or reconceptualize, novel formulation designs and dosing regimens.

Conceptually, long-term residence products are those that are applied and remain active for the duration of time during which the product (both the drug delivery system and the active pharmaceutical ingredient) remains in residence in the body. Most are familiar with a long-term residence product such as the contraceptive intravaginal ring, NuvaRing^®. This study supports the notion that a long-acting semi-solid formulation (i.e., not necessarily a long-term residence product) that would remain effective for several days might also be a viable option women would consider. Our findings suggest that the parameters of perceptibility and dimensions of acceptability regarding long-acting products are distinct from daily use or peri-coital products, as well as distinct from long-term residence products. There appears to be the potential for our conceptual understanding to include a continuum of duration of effectiveness that can span hours to days to weeks or even months. The user’s sensory perceptions and experiences of the biophysical properties of a long-acting product potentially would persist longer than in previously evaluated products. Because a semi-solid formulation would be in the body for longer periods of time, the experience of the product will likely change over time as the product interacts with vaginal fluids, body temperature, and potential hormone-affected changes in the vaginal environment. These factors need to be considered as dosing regimens are evaluated and user needs are targeted.

There is a clear contrast between what users consider “long-term residence” products and what we term “long-acting” products. Long-acting products differ from long-term residence products in that the product vehicle is not necessarily in residence in the vagina throughout the duration for which the drug confers protection. Once applied, this theoretical product allows the active pharmaceutical ingredient to perfuse into the target tissues where it remains active even after the product vehicle has eroded and been discharged from the vagina. Thus, the long-acting function is conferred by the active pharmaceutical ingredient, not the vehicle. An example of such a product would be an antiretroviral-based microbicide that accumulates in target tissues across time, and/or that has a prolonged half-life in target tissues, but is delivered intermittently via a semi-solid dosage form.

Among this sample of women, an apparent continuum existed with respect to how they conceptualize these products and their potential for use. The continuum blurs with the users’ understandings between long-term residence products and long-acting products, and requires further elaboration and consideration. On one end of the continuum are per-event, peri-coital (short-acting) products that are applied relatively close in time to a risk event (i.e., unprotected sexual intercourse), the effect of which is measured in hours (e.g., one to several hours). On the other end of the continuum are long-term resident, sustained-release products that are designed to release drug at a predetermined, consistent rate for a specified period of time, with the drug delivery system present throughout. This would include such drug delivery devices as the intravaginal ring (those lasting from one to several months, and up to a year), but could, theoretically, include semi-solid formulations that endure longer than the several hour threshold of a peri-coital product, potentially for several days. This latter theoretical formulation category better reflects the data presented here. The possibilities that fall within the continuum become more complex by conflating duration of pharmaceutical effect and duration of residence of the drug delivery system. Those that are more frequently administered (e.g., repeated daily dosing) maintain a state of prevention (i.e., a prevention concentration level) as a function of pharmaceutical half-life in the tissue, but either require repeated doses prior to a risk event to attain effective prevention concentration levels, or require repeated dosing to maintain this concentration level, or both. Those that are episodically administered confer a relatively immediate and longer duration of protection, but only when needed (e.g., a one-time use tablet that protects for 24 hours).

This continuum has implications for the design of products for HIV prevention, as well as multipurpose technologies. In particular, it suggests that a semi-solid formulation that is ineffective at one point in the continuum, for example, as a peri-coital product, could be effective at another point in the continuum (e.g., as a daily use or intermittent use formulation), and vice versa. For instance, it was clear from our data that participants felt that a “thick” (i.e., relatively high viscosity) gel would not be an optimal choice for a peri-coital product, because of the viscosity’s presumed interference with sexual pleasure. However, a future direction for microbicide and MPT research could be to evaluate whether a high viscosity gel that delivers an active pharmaceutical ingredient to the vaginal tissue across time as it dilutes slowly, being undetected in daily use, could be a choice for some women in the prevention of HIV or other reproductive health risks. This long-acting product could prevent infection without being perceived as a foreign object in the body, as a long-term resident device might be perceived. Thus, by considering various combinations of physicochemical and rheological performance properties of formulations across time, in parallel with dosing frequency options (and/or residency) and drug concentration targets, biomedical prevention product developers can rationally design the product that best suits the needs of drug efficacy and the needs of user experience.

Design of topical vaginal microbicides, and other biomedical prevention technologies, requires a balancing of formulation properties and performance, including: (1) effectively delivering drug to the vaginal vault, and (2) optimizing the user experience in an effort to potentiate and maintain use. Key research questions stemming from the present study that could be answered by future studies include whether a formulation's suboptimal characteristics as a daily use product may be more tolerable as a long-acting product, given their inherently more transitory nature in the later dosing regimen, and whether those same undesirable characteristics continue to be a challenge to adherence, even if the experience only lasts for a short amount of time. In addition, future inquiries could consider whether a long-acting product faces challenges with respect to perceived product efficacy if a user cannot “trust” that the active pharmaceutical ingredient was effective, because of the lack of physical evidence corroborating the drug’s presence once the vehicle is absent. Additional future research questions include: 1) Would users trust the efficacy of a long-term resident product’s active ingredient, based solely on the perception that the drug delivery system (i.e., device) remains, or could they trust long-acting product’s without benefit of the presence of a form or device?; 2) At what point in time do users begin to question their need for, or the efficacy of, a long-term resident product?; 3) Might a long-term residence product (or a long-acting product) potentially reduce effective dosing if users forget subsequent doses as the length of time between doses increases? These and other questions require consideration as new drug delivery systems are developed both for HIV prevention and for multipurpose technologies (i.e., products that prevent two or more negative consequences of sexual risk behavior, such as HIV, STIs, unintended pregnancy).

Our findings suggest that long-acting gels as drug delivery systems could be designed to optimize the user experience and might expand the HIV prevention “tool box” for women. For example, it is possible that a less frequent dosing regimen might increase overall adherence to such prevention products. Remembering to administer a weekly dose might prove more manageable than a daily dose or a coitally-associated dose. As another example, if it were determined that long-acting gels could be formulated in higher viscosity, lower volume gels to accommodate dilution over time, and utilizing “long-acting” drug transport via nanotechnology, the less desirable aspects of vaginal gel dilution and spreading (e.g., leakage) might be mitigated, thereby increasing positive perceptibility characteristics and leading to greater acceptability.

Formative research, such as the present study, has potential limitations. First, although our sample included women with a variety of previous and current vaginal gel/lubricant experiences, our findings may not be generalizable to potential users who do not have a previous history with vaginal gels/lubricants. Our sample was limited to women of reproductive age (18–45 years old) who were sexually active, not currently pregnant, and living in the northeastern United States. In addition, we did not assess women's self-perceptions of HIV-risk, making it difficult to know if these women perceived themselves to be at high risk for HIV acquisition. Generalization of our findings to populations with different characteristics would need to be evaluated. These data illuminate some of the challenges still to be addressed in drug delivery system development, for intravaginal dosing of both microbicides and MPTs.

Our findings are among the first to elucidate the differences in how potential users understand the concept of “long-acting” versus “long-term residence” characteristics, and to describe the concerns and possible challenges inherent in the potential acceptability of a long-acting (versus a long-term resident) topical vaginal formulation for HIV prevention in women. A major strength of this study is that we are able to report on women’s perceptions of a long-acting vaginal gel prior to its development, allowing potential users to provide specific feedback and input in the earliest stages of development. Understanding the characteristics of what women want, or do not want, in a long-acting vaginal gel could save developers time and resources required to develop novel drug delivery systems that women are willing to use. Considering these limited resources, it is advantageous to evaluate both the opportunities and challenges to use early in the development process. In addition, we advance the field of microbicide research by articulating the distinction potential users make in their consideration of long-acting products versus long-term residence products.

Conclusions

Consideration of the results of this study can expand the potential range of drug delivery systems with respect to microbicide and MPT development. While further studies regarding less frequent, coitally-independent dosing regimens are needed, our findings demonstrate that both long-term resident and long-acting products may be well-received among potential users, as the challenges of daily or coitally-associated use can be mitigated or eliminated.