Prospective acceptability of a multipurpose technology (MPT) implant in preclinical development to prevent HIV and unplanned pregnancy: Qualitative insights from women end users and health care providers in South Africa and Zimbabwe.

BACKGROUND: Given the high rates of both HIV and unintended pregnancies in sub-Saharan Africa, the SCHIELD program aims to develop a multipurpose technology implant for HIV and pregnancy prevention. An end-user evaluation was undertaken with young women and health care providers to assess preferences for modifiable implant attributes to improve future adoption and rollout. METHODS: Focus group discussions were conducted with potential women end users, and health care providers experienced in implant insertion or removal participated in in-depth interviews. All participants were recruited from Harare, Zimbabwe, or Soshanguve, South Africa. The purposively stratified sampled women were either implant experienced or implant naïve and were categorized into three groups: nulliparous, postpartum, or engaged in transactional sex. Topics covered included duration (six months to three years), biodegradability, removability, and independent rod retrievability (per indication). Data were analyzed using Dedoose software and summarized into emerging themes. RESULTS: Participants identified three key areas that could facilitate rollout, uptake, and adherence of an implant for HIV and pregnancy prevention. First, discreetness was the most salient topic and was associated with implant characteristics such as anatomical location, flexibility, and biodegradability. Second, the ability to independently retrieve the HIV or pregnancy prevention component was preferred, as life circumstances may change and was favored by all participants, except for young women in Soshanguve. Third, there is a need for proper counseling, sensitization, provider training, and health campaigns to facilitate rollout of a 2-in-1 implant. CONCLUSIONS: A 2-in-1 implant was seen as highly desirable by most young women and health care providers. Participants discussed potential concerns and barriers to uptake of a biodegradable implant with dual HIV prevention and contraceptive properties, identifying key implant attributes that product developers can modify while still in preclinical stages.

Incorporating end-users' voices into the development of an implant for HIV prevention: a discrete choice experiment in South Africa and Zimbabwe.

BACKGROUND: Input from end-users during preclinical phases can support market fit for new HIV prevention technologies. With several long-acting pre-exposure prophylaxis (PrEP) implants in development, we aimed to understand young women's preferences for PrEP implants to inform optimal design. METHODS: We developed a discrete choice experiment and surveyed 800 young women in Harare, Zimbabwe and Tshwane, South Africa between September-November 2020. Women aged 18-30 years who were nulliparous, postpartum, or exchanged sex for money, goods or shelter in prior year were eligible; quotas were set for each subgroup. The DCE asked participants to choose between two hypothetical implants for HIV prevention in a series of nine questions. Implants were described by: size, number of rods and insertion sites, duration (6-months, 1-year, 2-years), flexibility, and biodegradability. Random-parameters logit models estimated preference weights. RESULTS: Median age was 24 years (interquartile range 21-27). By design, 36% had used contraceptive implants. Duration of protection was most important feature, with strong preference for a 2-year over 6-month implant. In Zimbabwe, the number of rods/insertion sites was second most important and half as important as duration. Nonetheless, to achieve an implant lasting 2-years, 74% were estimated to accept two rods, one in each arm. In South Africa, preference was for longer, flexible implants that required removal, although each of these attributes were one-third as important as duration. On average, biodegradability and size did not influence Zimbabwean women's choices. Contraceptive implant experience and parity did not influence relative importance of attributes. CONCLUSIONS: While duration of protection was a prominent attribute shaping women's choices for PrEP implants, other characteristics related to discreetness were relevant. Optimizing for longest dosing while also ensuring minimal detection of implant placement seemed most attractive to potential users.

Engaging study participants in interpreting results: lessons from the TRIO study in Kenya and South Africa.

Background: Women account for 56% of new HIV infections in sub-Saharan Africa. Multipurpose Prevention Technologies (MPTs) are promising interventions because they combine HIV prevention with a less stigmatizing indication, such as pregnancy. We conducted a study with three placebo-only MPT products in Kisumu, Kenya and Soshanguve, South Africa, to assess preferences for attributes of tablets, vaginal rings and injectable products for dual prevention of HIV and pregnancy (TRIO Study). Here, we present former TRIO participants' views on the study results. Methods: After study completion in 2017, we held five dissemination sessions (two in Kisumu and three in Soshanguve) and five one-on-one sharing sessions in Soshanguve. Key results were discussed, with a focus on why some study products were more popular than others, which findings were surprising and why some women changed products over time. A thematic approach was used for analysis. Results: All 277 TRIO participants were telephoned, 168 (60.6%) were reached and 117 (42.2%) attended the dissemination sessions: 71 in Kisumu and 46 in Soshanguve. Participants were engaged and interested in the TRIO findings and willingly shared their perspectives and views candidly. Ease of use, discretion and familiarity were highlighted as drivers of product choice whereas novelty presented a challenge. In explaining the discrepancy between preference ratings and choices, participants cited features such as tablets being easy to explain to a partner or to discontinue. In explaining why 20% of participants switched products after practical experience, issues related to relationships with partners and product attributes perceived as unfavorable were paramount. Conclusion: The dissemination sessions provided an important forum for study participants to interrogate and explain the results to minimize possible misinterpretation. This exercise helped give context to the results, ensured correct lessons were derived from those results and increased credibility of the findings reported by the investigators.

Two Birds with One Stone: Health Care Providers' Perspectives about Prevention Technologies in Kenya and South Africa.

To meet the reproductive health needs of women, especially those in sub-Saharan Africa, multipurpose prevention technologies (MPTs) that combine pregnancy and HIV prevention into a single product could be highly beneficial. This qualitative study with health care providers in Kenya and South Africa examined health system factors that may facilitate or inhibit the delivery of these MPTs. Twelve qualitative interviews were conducted with health care providers at each site (24 interviews total). Providers were presented with pictures and actual placebo prototypes of 4 MPTs: a vaginal ring, an oral pill, an injectable, and an implant. Four themes emerged related to health care providers' reported interest in offering the proposed MPTs: (1) perceptions of young women's interest in the MPTs, (2) considerations about product administration, (3) feedback about product attributes, and (4) providers' training needs. Overwhelmingly, health care providers are eager to offer a product that prevents both HIV and unintended pregnancy in young women.

"We are not the same": African women's view of multipurpose prevention products in the TRIO clinical study.

PURPOSE: Unintended pregnancy and HIV infection present dual risks for young women in sub-Saharan Africa. New multipurpose prevention technologies (MPTs) are in development to simultaneously prevent unintended pregnancy and HIV, but there is a need for end-user research to ensure these products suit women's needs. The Tablet, Rings and Injectables as Options (TRIO) for women study took place in Kisumu, Kenya, and Soshanguve, South Africa, with the goal of eliciting young women's feedback on three potential MPTs. METHODS: Women in TRIO used three placebo products that represented potential MPTs: daily oral tablets, monthly vaginal rings, and monthly dual injections in a randomized crossover design followed by a period in which they chose a product to use. Eighty-eight TRIO participants completed in-depth interviews and focus group discussions to understand their experiences using each product. Qualitative analyses were conducted after stratifying by product preference at the end of the crossover period. RESULTS: The majority (65%) of participants preferred injections, with the remainder evenly split between tablets and rings. Discussions of preference for one product were closely linked with expressed dislike of another product's attributes. Participants recognized heterogeneity in preferences and choices across users and stressed the need for multiple MPT options that confer a low burden on women's daily lives. CONCLUSION: Rather than choosing a product to use based on the product's perceived advantages, women's choices were based on the unfavorable attributes of other TRIO products. Moreover, the importance that women placed on a given disadvantage varied. Disadvantages that women deemed as most important emerged as a greater driver of product preference than selecting products based on their advantages and favorable characteristics.

Perspectives of South African youth in the development of an implant for HIV prevention.

INTRODUCTION: Implants are a new dosage form in development for HIV pre-exposure prophylaxis (PrEP) with potential for high adherence given that they are provider-administered and are intended for long-acting protection. Integrating end-user preference into early stage product development may further overcome challenges with future product uptake and adherence. Hence, we sought to optimize the design of a PrEP implant in early-stage development by gathering opinions about implant attributes from potential end-users in South Africa. METHODS: We conducted 14 focus group discussions (FGDs) with young women and men aged 18 to 24 in Cape Town and Soshanguve, South Africa, inviting participants into discussion as co-designers. FGDs were homogenous by gender and previous implant experience. During FGDs, we showed prototype devices and followed a semi-structured guide with questions on history of contraceptive implant use, preferences for physical characteristics of an implant, implant biodegradability, insertion process, participant-driven ideas for implant design, and social adoption considerations. FGDs were facilitated in English, isiXhosa, Tswana, isiZulu, or Tsonga, audio-recorded, transcribed into English, and qualitatively coded and analysed. RESULTS: In this qualitative sample of 105 youth (68 women and 37 men), 58 participants were from Soshanguve and 47 from Cape Town, and 23% had previously used contraceptive implants. Participants expressed preferences for several implant design features; specifically, longer duration (≥6 months) was more important to most participants than the size or number of devices implanted. A majority preferred a flexible versus stiff implant to minimize palpability, thereby increasing discreetness and comfort. Nearly all participants favoured a biodegradable implant to avoid removal and thus reduce clinic visits. Concerns about the implant centred on its possible side effects and the "plastic" look of the prototype displayed for demonstration. CONCLUSIONS: This study offers preliminary insights into an implant for HIV prevention that provides long-lasting protection may be well received among young South Africans. Additionally, flexibility, discreetness, and biodegradability may increase acceptability of the implant. Such end-user feedback is being incorporated into current implant designs in the hope of creating an effective long-acting PrEP product that is likely to achieve high uptake and adherence in target populations.

"It Was Not My Aim to Sleep There": The Impact of Timing and Location of Sex on Adherence to Coitally-Dependent HIV Pre-exposure Prophylaxis.

The FACTS 001 trial found that vaginal pre- and post-coital application of 1% tenofovir gel did not prevent HIV-1 infection amongst young South African women. The trial included a multi-faceted approach to adherence support and collected objective and self-reported adherence measures. Using qualitative data collected from a random sub-set of FACTS 001 participants (135 in-depth interviews at product discontinuation and 13 focus group discussions at dissemination of trial results), we explore the importance of 'place' and 'timing' in shaping acts of sexual intimacy and product adherence. Demographically, this qualitative sub-sample is similar to the trial cohort of predominantly young, unemployed women living with parents or other family members. Sexual intimacy was largely unpredictable and happened across multiple locations in which women had limited privacy, autonomy, or control over the timing of sex. This made adherence to the dosing strategy challenging. Findings may inform the development of future event-driven pre-exposure prophylaxis regimens or products.

Young Women's Ratings of Three Placebo Multipurpose Prevention Technologies for HIV and Pregnancy Prevention in a Randomized, Cross-Over Study in Kenya and South Africa.

End-user input is critical to inform development of multipurpose prevention technology (MPT) products that prevent HIV and pregnancy. The TRIO Study, conducted in Kenya and South Africa, enrolled 277 HIV-negative women aged 18-30 in a randomized cross-over study to use each placebo MPT (daily oral tablets, monthly injections, and monthly vaginal ring) for one month. At the end of each month, participants rated how much they liked using the product on a 5-point Likert scale (5 = liked very much). We compared mean ratings using paired t-tests and examined sociodemographic-, attribute-, and behavior-related characteristics associated with ratings using multivariable linear regression and data from in-depth interviews. After use, mean ratings were significantly higher for injections [4.3 (SD = 1.0)] compared with tablets [3.0 (SD = 1.3)] and rings [3.3 (SD = 1.4)] (p < 0.001); mean ratings for rings were significantly higher than for tablets (p = 0.013). Mean ratings of a hypothetical active MPT increased for all products after the one-month period of use, with the greatest increase for rings, the least familiar product. In multivariable analysis, acceptability of key product attributes (e.g., product look) were associated with a significant increase of ≥ 1 point in the mean rating across all three products (p ≤ 0.001). Perceived ability to use the product without partner knowledge was associated with a higher mean rating for rings (b = 0.50; p = 0.006). The acceptability of product attributes contributed significantly to the rating of all products, highlighting the value of choice in pregnancy and HIV prevention to accommodate diverse users.

The Tablets, Ring, Injections as Options (TRIO) study: what young African women chose and used for future HIV and pregnancy prevention.

INTRODUCTION: Preventing HIV and unintended pregnancies are key global health priorities. To inform product rollout and to understand attributes of future multipurpose prevention technologies (MPT) associated with preference and use, we evaluated three placebo delivery forms: daily oral tablets, a monthly vaginal ring, and two monthly intramuscular injections in TRIO, a five-month study among young Kenyan and South African women. METHODS: HIV-negative, sexually active, non-pregnant women aged 18 to 30 were enrolled and randomized to use each placebo delivery form for one month (stage 1). Then, participants chose one product to use for two additional months (stage 2). We assessed safety, product ranking, choice, and use. We examined demographic and behavioural correlates of choice and, reciprocally, unwillingness to use in the future with logistic regression models. RESULTS: 277 women enrolled, 249 completed stage 1 and 246 completed stage 2. Median age was 23 years, 49% were Kenyan and 51% were South African. Three participants became pregnant during the study and one participant HIV-seroconverted. There were 18 product-related adverse events, six tablets-related, 11 ring-related, and one injection-related. After trying each product, 85% preferred a TRIO product over condoms. Injections were chosen most (64%, 95% confidence interval (CI) 58%, 70%; p < 0.001), and by more South Africans than Kenyans (odds ratio (OR) 2.01, 95% CI: 1.17, 3.43; p = 0.01). There was no significant difference in choosing tablets versus ring (21%, 95% CI: 16%, 26% vs. 15%, 95% CI: 11%, 20%; p = 0.11). Tablet and ring adherence, based on direct observations and self-reports, improved over time. However, participants' self-reported use of tablets did not match objective data from the electronic dose monitoring device. Participants were fully compliant with injections. CONCLUSION: In this population at risk for HIV and pregnancy, all participants agreed to choose and use a placebo MPT delivery form. A majority of participants preferred TRIO products to male condoms, an existing MPT. Injections were most liked and best used, however, they are years away from reaching the clinics. In the meantime, expanding the availability of tablets and giving access to rings can begin to fulfill the promise of choice for HIV prevention technologies and inform the development of suitable delivery forms as MPT.

End-Users' Product Preference Across Three Multipurpose Prevention Technology Delivery Forms: Baseline Results from Young Women in Kenya and South Africa.

A multipurpose prevention technology (MPT) that combines HIV and pregnancy prevention is a promising women's health intervention, particularly for young women. However, little is known about the drivers of acceptability and product choice for MPTs in this population. This paper explores approval ratings and stated choice across three different MPT delivery forms among potential end-users. The Trio Study was a mixed-methods study in women ages 18-30 that examined acceptability of three MPT delivery forms: oral tablets, injections, and vaginal ring. Approval ratings and stated choice among the products was collected at baseline. Factors influencing stated product choice were explored using multivariable multinomial logistic regression. The majority (62%) of women in Trio stated they would choose injections, 27% would choose tablets and 11% would choose the ring. Significant predictors of choice included past experience with similar contraceptive delivery forms, age, and citing frequency of use as important. Ring choice was higher for older (25-30) women than for younger (18-24) women (aRR = 3.1; p < 0.05). These results highlight the importance of familiarity in MPT product choice of potential for variations in MPT preference by age.

Identifying factors that influence pregnancy intentions: evidence from South Africa and Malawi.

In developing-country settings, pregnancy intentions are often assessed using a series of questions from the Demographic and Health Surveys, yet research conducted in several countries yields conflicting results regarding these questions' ability to predict pregnancy. Conducted in Malawi and South Africa, this study identified individual, partner and societal factors that influence desire for pregnancy, and women's ability to achieve their intentions. Data come from interviews and focus-group discussions conducted prior to the FEM-PrEP HIV-prevention trial with women from communities at high risk of HIV infection. Cultural norms regarding contraceptive use and childbearing influenced both women's desire for pregnancy and ability to achieve those goals. Partner's expectations for pregnancy, financial concerns, family composition and contraceptive experiences were additional influences. Actively planning for pregnancy was not a salient concept to the majority of participants. Results support the call for a multidimensional measure of pregnancy intention that reflects the variety of factors that influence intentions, highlight the fluid nature of many women's reproductive health decision making and challenge the notion that all fertility decisions are the result of conscious action. Additional work on how women's plans for pregnancy are achieved would be programmatically more useful than current measures of intention.