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Prevention Research

The Invisible Product: Preferences for Sustained-Release, Long-Acting Pre-exposure Prophylaxis to HIV Among South African Youth

Montgomery, Elizabeth T. PhDa; Atujuna, Millicent PhDb; Krogstad, Emily PhDa; Hartmann, Miriam MPHa; Ndwayana, Sheily BAb; O'Rourke, Shannon MPHa; Bekker, Linda-Gail PhD, MDb; van der Straten, Ariane PhDa,c; Minnis, Alexandra M. PhDa,d

Author Information
JAIDS Journal of Acquired Immune Deficiency Syndromes: April 15, 2019 - Volume 80 - Issue 5 - p 542-550
doi: 10.1097/QAI.0000000000001960



The field of HIV prevention has made notable recent progress through the established safety and effectiveness of oral pre-exposure prophylaxis (PrEP)1,2 and the safety and partial effectiveness of a topical microbicide vaginal ring.3,4 Although these technologies provide valuable prevention options, users of both have faced adherence challenges.3,5,6 PrEP approaches that are long-acting (eg, 2–3 months or longer) are at earlier stages of development and aim to overcome some of the documented challenges with uptake and adherence to current prevention methods.7 Partially in response to clinical trial failures,8–10 there is enhanced appreciation for end-user research during preclinical and early clinical stages of product development, to identify and potentially modify features of a method that might increase its chances for successful adoption and, consequently, its public health impact.

Youth in HIV endemic settings such as South Africa are a key end-user population for long-acting methods because of their increased risk of HIV acquisition and their documented challenges with adherence.11 Young people have distinct risk profiles shaped by partner characteristics and partnership patterns, relationship power imbalances, and limited access to confidential, youth-friendly sexual health services.12,13 Furthermore, young people experience unique social and structural influences (eg, family environment, community stigma, and health delivery system constraints) that, in addition to dynamic neurocognitive development,14–16 shape risk perception and adoption of HIV prevention practices. In South Africa, many youth face additional challenges presented by impoverished living conditions, high unemployment, community violence, and sociocultural tensions between traditional and modern urban life.17 Indeed, research studies exploring the acceptability of novel HIV prevention strategies before dissemination have highlighted the complexity of young people's lives in this setting.6,18,19 This article presents findings from one of the first studies to explore the attitudes and preferences of young male and female South African end-users regarding long-acting sustained-release HIV prevention approaches formulated as injections or implants. Given that youth constitute a key target group for these products, examining their perspectives is essential to inform product development in ways that might enhance adoption and use.


Study Design and Setting

The iPrevent study is a 2-stage research study using both qualitative and quantitative methods to identify aspects of long-acting PrEP that are important to male and female South African youth aged 18–24 years. In-depth interviews (IDIs) and focus group discussions (FGDs) were conducted to identify individual, social, and structural factors believed to affect PrEP uptake and adherence. Participants were primarily recruited from 2 clinical site catchment areas in Cape Town: Emavundleni, a high-density township approximately 21 km east of the City Center, and Masiphumelele, a more remote township on the Cape Peninsula, approximately 38 km south of the City Center.

Study Sample

To ensure participants could provide opinions rooted in actual experience, youth who had previous experience with a range of products (either the active or placebo version of the dosing platform) were purposively selected. For IDIs, the target sample included men who had participated in an oral PrEP study and women who had experience using oral PrEP; sustained-release antiretroviral (ARV) PrEP (eg, the monthly dapivirine ring); or injectable PrEP (Table 1). Participants exiting from the designated trials who were HIV negative at trial exit, met the age criterion, and gave permission to be contacted for future studies were eligible for recruitment. For enrollment, participants who reported current sexual activity (vaginal or anal sex at least 3 times in the last 3 months) and who were currently 18–24 years old were eligible. For FGDs, participants were purposively recruited at the 2 clinical sites through former study participant rosters and community outreach according to the following criteria: (1) females who had experience using a contraceptive implant (eg, Implanon NXT or Jadelle), (2) females with no previous implant experience, and (3) males. Sexual orientation was not a criterion for FGD grouping; however, because of recruitment source, one male FGD comprised men who have sex with men (MSM) only (n = 7) and the other was entirely heterosexual (n = 10).

Distribution of Previous PrEP and Contraceptive Method Experience, by Gender and Interview Type

Data Collection

The design of IDI guides was informed by a socioecological framework,20,21 which incorporates the influence of factors at the individual, interpersonal, and structural levels, and has been used in several previous HIV prevention studies to understand product acceptability and use.6,22–24 Questions explored individual narratives about HIV and HIV-risk perceptions, partner characteristics and patterns, living situations, and sexual behavior, and how these influenced youth's interest in and use of PrEP. Interviews solicited impressions on long-acting injectables and implants, and perceptions of these products relative to the PrEP method(s) they previously used. In addition, youth's perceptions of health care providers and facilities, and social norms—including stigma—around young people and sex, HIV and risk behavior were explored. During IDIs, participants were shown a pictorial tool that contained pictures of existing family planning and HIV prevention methods, with a description of key product features. This tool was used to explore knowledge of, attitudes toward, and experiences with different delivery forms, and to discuss specific product attributes of each approach. IDIs with male and female youth were conducted at research clinic sites in English or isiXhosa by trained South African social scientists. All interviewers were female; for males, comfort with a female interviewer was confirmed as part of the screening and/or informed consent processes, before data collection, and no men declined participation.

FGD guides concentrated on the implant as a long-acting method, with particular emphasis on obtaining feedback on prototypes of a biodegradable thin-film polymer device being developed for HIV prevention.25,26 Topics covered included personal experience with and community perceptions of contraceptive implants, physical attributes of PrEP implants in development (eg, size, duration, flexibility, and biodegradability), insertion process, and social adoption factors (eg, discreet use and service delivery). During FGDs, participants were shown pictures and examples of contraceptive and prototype HIV preventative implants and applicators for insertion, and were able to handle them.27 The pictorial tool used in IDI was also shown. FGDs were cofacilitated by a biomedical engineer from the United States and a South African social scientist, using a combination of English and isiXhosa. Interview guides and pictorial tools for IDI and FGD are available in the supplementary materials,


Interviews were audio-recorded, transcribed, and translated (if applicable). Interview transcripts were reviewed for clarity and queried by analysts on the protocol team. Once finalized, they were uploaded into Dedoose software (v 7.5.9—v 7.6.23). IDI transcripts were coded using a structured codebook that was iteratively developed by a multinational coding team. At the beginning of coding, 2 transcripts were triple-coded (independently coded by each of the 3 coding team members) and discrepancies discussed. Throughout the process, the team evaluated inter-rater reliability (IRR) and had regular (eg, weekly) meetings to resolve disagreements in code applications and to refine the codebook. FGD transcripts were coded using a modified version of the IDI codebook. Two IRR tests were taken throughout the coding process, and disagreements in code applications were resolved by consensus.

For this analysis, key codes related to study product preferences were summarized by participant group. Further iterative review of code reports was performed to thematically organize and interpret the dominant themes of the data within the conceptual framework of a socioecological model.21

Ethical review committees from each collaborating institution provided oversight to the conduct of this research.


Study Population

A total of 95 participants, of whom 62 were female and 33 male, completed 50 interviews and 6 FGDs. FGD groups ranged in size from 4 to 10 participants (median 8). Participants were, on average, 22 years old, 15% of the sample identified as heterosexual male, 63% heterosexual female, and 20% MSM. Ninety-one percent were in a relationship, but only 1% were married. The majority (94%) described themselves as Xhosa. Approximately two-thirds (63%) of the study sample had completed secondary school and one-third attended some college. Nevertheless, less than half (48%) received any income, including social grants. Approximately half the men and a quarter of the women also reported casual partners; half (47%) indicated that they knew or suspected that their main partner had another partner. Condoms were reportedly used during the last sex episode by 61% of respondents (Table 2).

Select Study Population Characteristics (n = 95)

By design, all IDI participants had previous PrEP research-study experience, including 18 men and 22 women who had used oral PrEP; 12 women who had used injectable PrEP and 10 women who had used a vaginal ring (Table 1). In addition, most women (82%) had experience using an injection for contraception or HIV prevention. Twenty-one (35%) women had experience using an implant for contraception.

End-User Experiences With and Attitudes Toward Short- and Long-Acting HIV Prevention

Male and female youth in IDIs shared positive and negative feedback about attributes of each dosing formulation they had tried for HIV prevention.

Among women who had used the vaginal ring, feedback was most frequently about product efficacy, and half of the women expressed an interest to use it in the future if it was protective. Participants also commented on physical attributes (size and hardness), cost, side effects, and intravaginal administration. Most discussion about use experiences reflected feelings about and experiences with using the ring during sex and whether or not partners would notice it—whether she had disclosed or not disclosed ring use to a partner. Women reported that some removed the ring before sex, so that partners would not feel it. One participant worried that the ring could potentially come out and cause embarrassment. She believed that an injection would overcome this issue, and that it might allow her greater sexual freedom and pleasure:

There is nothing I would change about the ring except that it is an embarrassment for example I am having sex with my boyfriend or casual partner and the ring gets attached on his penis and comes out whilst having sex, it’s an embarrassment […] Because once an injectable is injected and it won’t embarrass you. Even if you sleep with a boyfriend you will sleep with free pleasure… It won’t be attached on his penis. I will get my injection at the clinic, go out partying or sleep with whomever I like. (IDI #2003, ring-experienced female, age 23).

Oral PrEP-experienced men often described the daily dosing regimen of pills as challenging. Pills were described as forgettable and difficult to use on weekends and at the same time each day. Several men expressed a desire for something that simply lasted longer in their system.

I wouldn’t mind using it Friday when I go out and Saturday when I go out, maybe Sunday if I'm going out. …you know that maybe Friday, Saturday and Sunday you might get lucky [laughing]….I want to use it and it stays in my system for a very long time….As a 100%… (But) I hate the daily intake. (IDI #1105, male oral PrEP-experienced, age 24).

The fact that the pill dissolves and gets into your system (vs. male condoms) was viewed as a benefit; however, the pill size was problematic because it was perceived to take a long time to absorb and be effective, and to be challenging to swallow. One man suggested the PrEP pill should be made to dissolve in liquid, both to minimize the challenge of swallowing, and make it less like an ARV pill for treatment. In some cases, the pills were described as embarrassing and linked to being HIV positive, necessitating secrecy to avoid stigmatization.

By contrast, some female oral PrEP users stated that pills were more discreet than other methods, for example, they do not leave a mark like an injection. Like some oral PrEP-experienced men, women who had used these products highlighted the benefit of the pill working systemically; it won’t break like a condom, it does not interfere with sexual pleasure, nor do you have to think about it during sex. Nevertheless, others disfavored the comparatively short duration of protection that the pill offered.

Injectable-experienced women appreciated not having a daily product and felt that receiving the injection every 2 to 3 months was feasible. The injection was perceived to provide greater protection because it would be absorbed in their bodies, they would not forget to take it (like pills), and it would not burst (like condoms). Experience of side effects (eg, headache, dizziness, and nausea) was raised as the main complaint with using injectable PrEP. Some participants stated that injection site pain was also a negative aspect but acknowledged that the pain was temporary and soreness subsided within a day or 2.

Preferences for HIV Prevention: The Invisible Product

Irrespective of previous method-use experience, gender, or sexual orientation, most participants expressed a preference for prevention methods formulated as injectables or implants. Several participants mentioned that their top priority in any product was efficacy. For some, high efficacy would override the importance of all other attributes. For example, even if they feared the pain, they would use an implant or an injectable as long as it was fully protective. Although efficacy was a top priority, there was also a clear desire across all subgroups for an “invisible” product that would not interfere with sex, that would stay in the system to provide protection, that caused minimal user burden, or that was not apparent to others, and these characteristics were most salient for long-acting methods. As explored below and depicted in Table 3 with illustrative quotes, narrative explanations for preferences converged thematically around different dimensions of “invisibility” that reflect a socioecological framework, including invisibility to oneself, one's partner and household members, community members, and outsiders.

Preferences for Sustained-Release Long-Acting Products by Theme, With Illustrative Quotations

Invisible to Oneself

Data about invisibility to oneself included preferences for the systemic nature of long-acting methods: that they were relatively simple and effortless (low user burden), did not require frequent administration (longer acting), and were perceived as more efficacious, which, as mentioned above, was the attribute of overarching importance to these young people. Participants favored a method that was pain free with no side effects—another aspect of being invisible or unnoticeable. In addition, several participants expressed appreciation for a product that remains in the system because it provides more reliable coverage (or full protection) without worry of missed doses, a common occurrence among youth.

Hence, having a product that was physically invisible to oneself was important. When discussing the implant, for example, men in particular, described wanting a more flexible and less palpable implant, so that they would not be constantly reminded that a foreign object was in their body. On the other hand, when discussing the biodegradable implant under development, many cautioned that this concept may not be easily understood, and that people would be concerned about where the dissolving implant goes into their body.

Invisible to Others

The invisibility of long-acting products to others was also a dominant theme; preferably, they would not be seen or felt by friends, family, or partners. Rather than the commonly used location of the upper arm, youth recommended administration to locations such as the thigh or stomach or another “hidden place”—somewhere less visible or palpable. Pertaining to the implant, participants commented that “It has to be small so it doesn't show,” and one woman said she would use the implant in the future for HIV prevention “as long as it is not going to swell and make a caterpillar [under the skin].” Another participant clarified that her preferred method would not require stitches. For some, implant rods were perceived as less “invisible” than injectables because someone might grab one's arm and feel it—thereby unintentionally disclosing its use (Table 3). FGD participants, who had more opportunity for interactive discussion and learning about implants, preferred a flexible (vs. stiff) rod to enhance discretion.

An HIV prevention method that did not necessitate disclosure to family or household members, and that was private, was another salient aspect of preference. In contrast to oral PrEP, long-acting methods were seen to provide greater discretion because a product did not have to be carried around, stored covertly in crowded households, or used in settings where parents were unsupportive. Methods were similarly regarded as offering greater discretion if product use had not been disclosed to partners. For some women, the systemic application and discretion of an injectable or implantable was described as preferable within partnerships where use of the ring had not been disclosed, or was disfavored. MSM described similar situations where a long-acting method would overcome “shyness” or fear to disclose pill use to a partner (Table 3).

Invisible to Community

Similar to fears about partners or family members discovering use of HIV prevention and the consequent implications about sexual behavior and/or sexuality, several participants expressed fears about community members learning of prevention method use. Long-acting methods offer enhanced discretion from community stigma because they required fewer trips to the clinic or pharmacy (which might suggest an HIV-positive status) and did not require transportation and storage of products.

Of note, community invisibility was also highly salient due to commonly cited stories about implants inciting robbery. Participants across all subgroups shared stories about contraceptive implants being physically cut out and removed from women's arms by gang members who wanted to smoke the drug in the implants (Table 3). One woman felt that the injection would be better for the community as a whole due to this fear, and others felt that softer and less-visible rods would help to address these concerns.


Sustained-release long-acting methods of HIV prevention, including ARVs formulated as injectables and novel biodegradable or removable implants, are a promising set of strategies in preclinical and clinical development. In addition to exceptional safety and efficacy, a critical hope and priority is that they expand the toolbox of options for individuals requiring or preferring less-frequent dosing. Young men and women in South Africa are arguably one of the most important end-user groups globally,11 and this research offers several important insights into their priorities and preferences for novel HIV prevention approaches. In this qualitative study, long-acting injectable and implantable methods were favored over oral PrEP and the dapivirine ring. Assuming that a novel product is highly efficacious, the most salient attributes favored among all HIV prevention methods, most strongly expressed by long-acting approaches, were related to invisibility. Youth wanted a product that necessitated the least amount of work and awareness; they did not want it to be seen or felt; they did not want to have to talk about it; and they wanted it to require minimal effort to maintain. Put more bluntly: although these end users may have recognized the importance of HIV prevention, they did not want it to burden their daily life.

A desire for invisibility was largely a function of lifestyle. Many youth described busy, active lives. They are not yet “settled down,” and move around—especially on weekends—to visit, socialize, and party. Most did not live with their partners, and many have multiple partners. Injections and implants were described as suitable for this dynamic lifestyle where daily methods might be skipped, forgotten, or raise suspicions. This finding is consistent with regional increases in the uptake of long-acting contraceptives among women (eg, increasing from 37% to 46% of modern method mix in sub-Saharan Africa from 2003 to 2012).28,29 Long-acting HIV prevention was also positively portrayed as endowing one with freedom to spontaneously have sex, worry-free, with whoever one might want. Although this type of sexual behavior has been a cause for concern in previous prevention method research, for example, men disapproving of microbicides for fear women will become “promiscuous,”30–33 it offers a realistic picture of the desires and activities of young people in this setting. It is pertinent to recognize that these young South Africans have lived their entire lives under the specter of an HIV-epidemic, and that these youth did not express a desire to sleep around without consequence, rather, a desire for greater freedom, and reduced anxiety around HIV.

The importance of community invisibility highlighted the fact that taboos around sex and HIV-related stigma continue to persist. Despite generations of people affected with HIV, youth were still wary of disclosing ring or oral PrEP use to partners, family, or community members because of what it might imply about their sexual behavior, their sexual orientation, or their disease status. Stigma is related to another aspect of this African research setting: many live in densely populated areas with minimal privacy in the community and in their homes.17 There is not the same degree of anonymity that may exist in other Western urban settings.34

The implant robbery anecdotes offer some important insights into introduction of novel technologies and the context of community violence in which this research was conducted. Rumors—whether based in truth or reality—are powerful. Implant robberies in Cape Town were reported in one online news story that we could identify35; several FGD participants reported personally knowing a victim. Nevertheless, many IDI and FGD participants—both male and female—mentioned the fear of implant robbery by gang members. The township in which many of these participants resided, Nyanga, has high rates of reported murder, physical and sexual assault, and crime.36 Although here participants expressed concern that the implant might induce violence, other research with MSM and women from these areas has highlighted that other novel technologies (eg, rectal microbicides and rings) are perceived to confer safety from HIV in a context of high sexual assault.18 These data reinforce the importance of evaluating, and potentially addressing, the role of rumors and other structural factors such as community violence, and their impacts, when doing research and programmatic activities with novel products.

Consideration of end users is important during product development. Both efficacy trials and rollout of effective biomedical HIV prevention technologies have encountered setbacks that—theoretically—may have been averted through research into end-user and health system determinants of uptake and use.37 When designing next-generation PrEP dosage forms, product developers could prioritize features that the potential end users in this study identified as important, such as a product that is long-acting and invisible by sight, by feel, and by packaging. In addition to traditional qualitative methods like these, other methodological approaches, for example, human-centered design and social marketing, can help to elucidate ways in which PrEP can be made more attractive and appealing, less burdensome to daily activities, and better aligned with youth's lifestyles.

There are several limitations to this research. IDI participants were purposively recruited from former PrEP clinical trials and are likely to be more knowledgeable and accepting about PrEP and HIV prevention than other South African youth. Although these participants candidly shared many concerns and complaints about current and future prevention approaches, it is unknown whether “research-naive” youth in the community would have shared the same attitudes. It is also unknown how acceptability for these products will change when actual products are available. Some FGD participants were recruited from the community-at-large, but most were recruited from former HIV or contraception-related studies. Participant reactions to implants may have been impacted by the length and content of the implant description in IDIs, which varied widely depending on the depth of questions raised by the participant. FGDs were facilitated by a bioengineer with laboratory experience in designing new PrEP technologies, and participants may have been biased (social desirability) to express favorable views toward implants. That said, participants expressed many of the same opinions in the absence of this facilitator. FGDs were homogenous by gender and previous experience of implants; however, males were not stratified by sexual orientation, which may have impacted responses regarding an HIV prevention product. That said, the FGD discussion topics focused more on HIV prevention product features than sexual behavior. Another potential limitation is that a male interviewer was not available; however, no men declined to participate because of this. As with all qualitative studies, our results may be biased by the exclusion of questions or probes that were not explored, and there may be misinterpretations of the data through various stages of analysis, including translation, coding, and summarization. We did not conduct member checking, whereby researchers validate their results with study participants. These limitations were mitigated by the inclusion of local scientists on the analysis and writing teams.

In conclusion, the young South Africans in this study expressed preferences for an invisible HIV prevention product—one that required minimal user burden; did not cause side effects; and could not be noticed by partners, family, friends, or community members. Long-acting sustained-release injectable and implantable methods were favored by most because of these desired features. An examination of specific product attributes influential to product preference in a generalizable sample of youth could inform product design and build on youth's interest in a product that is perceived to offer and achieve invisibility.


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South Africa; youth; PrEP; sustained-release long-acting PrEP; implants; injections

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