The role of economic evaluations in advancing HIV multipurpose prevention technologies in early-stage development.

Product development is a high-risk undertaking, especially so when investments are prioritized for low- and middle-income countries (LMICs) where markets may be smaller, fragile, and resource-constrained. New HIV prevention technologies, such as the dapivirine vaginal ring (DVR) and long-acting injectable cabotegravir (CAB-LA), are being introduced to these markets with one indication, meeting different needs of groups such as adolescent girls and young women (AGYW) and female sex workers (FSWs) in settings with high HIV burden. However, limited supply and demand have made their uptake a challenge. Economic evaluations conducted before Phase III trials can help optimize the potential public health value proposition of products in early-stage research and development (R&D), targeting investments in the development pathway that result in products likely to be available and taken up. Public investors in the HIV prevention pipeline, in particular those focused on innovative presentations such as multipurpose prevention technologies (MPTs), can leverage early economic evaluations to understand the intrinsic uncertainty in market characterization. In this perspective piece, we reflect on the role of economic evaluations in early product development and on methodological considerations that are central to these analyses. We also discuss methods, in quantitative and qualitative research that can be deployed in early economic evaluations to address uncertainty, with examples applied to the development of future technologies for HIV prevention and MPTs.

Key programmatic and policy considerations for introducing multipurpose prevention (MPT) methods: reflections from healthcare providers and key stakeholders in South Africa.

Introduction: Multipurpose prevention technologies (MPTs) simultaneously prevent HIV, other sexually transmitted infections, and/or unintended pregnancy. Key gatekeepers, [healthcare providers (HCPs) and key stakeholders] require proactive engagement before product implementation. This manuscript identifies HCP demand creation strategies, key stakeholder considerations for the adoption of MPTs in South Africa. Methods: Formative research was conducted in three districts in three South African provinces (July to November 2022). Nurses initiating oral PrEP at facility and mobile study sites participated in 4-hour participatory workshops, exploring HIV prevention, including MPTs, demand creation strategies, and preferred MPTs training packages. Activities were observed, transcribed, and thematically analysed. Five online in-depth interviews (IDIs) with Key informants (KIs) (National/district programme implementers and technical leads) and one in person, exploring key programmatic and policy considerations for MPT adoption. IDIs were approximately 40 min long, audio recorded, transcribed, and thematically analysed. Results: Twenty-one Professional Nurses completed workshops: 19 female. Six IDIs were conducted with 4 Facility Managers, 1 NDoH representative and 1 DoH Provincial Deputy Director. All participants were females, aged 30-60+ years with >10 years' in SRH/HIV policy/advocacy/research. Community conversations and information at the clinic were the best MPT demand creation methods among HCPs. KIs identified five considerations for future MPT implementation: HCP training; demand creation and messaging; existing PrEP policy amendments; preparing users for additional choice; and sustaining MPT provision. Conclusion: Contraceptive implant and oral PrEP implementation lessons learned should be proactively considered when preparing for MPT introduction. HCP training and demand creation are of particular importance before MPT introduction.

Pharmacokinetic Study of Islatravir and Etonogestrel Implants in Macaques.

The prevention of HIV and unintended pregnancies is a public health priority. Multi-purpose prevention technologies capable of long-acting HIV and pregnancy prevention are desirable for women. Here, we utilized a preclinical macaque model to evaluate the pharmacokinetics of biodegradable ε-polycaprolactone implants delivering the antiretroviral islatravir (ISL) and the contraceptive etonogestrel (ENG). Three implants were tested: ISL-62 mg, ISL-98 mg, and ENG-33 mg. Animals received one or two ISL-eluting implants, with doses of 42, 66, or 108 µg of ISL/day with or without an additional ENG-33 mg implant (31 µg/day). Drug release increased linearly with dose with median [range] plasma ISL levels of 1.3 [1.0-2.5], 1.9 [1.2-6.3] and 2.8 [2.3-11.6], respectively. The ISL-62 and 98 mg implants demonstrated stable drug release over three months with ISL-triphosphate (ISL-TP) concentr54ations in PBMCs above levels predicted to be efficacious for PrEP. Similarly, ENG implants demonstrated sustained drug release with median [range] plasma ENG levels of 495 [229-1110] pg/mL, which suppressed progesterone within two weeks and showed no evidence of altering ISL pharmacokinetics. Two of the six ISL-98 mg implants broke during the study and induced implant-site reactions, whereas no reactions were observed with intact implants. We show that ISL and ENG biodegradable implants are safe and yield sufficient drug levels to achieve prevention targets. The evaluation of optimized implants with increased mechanical robustness is underway for improved durability and vaginal efficacy in a SHIV challenge model.

Common ground: the opportunity of male contraceptives as MPTs.

Multipurpose prevention technologies (MPTs) and male contraceptive methods are currently in development to address unique and critical needs facing the global reproductive health community. Currently, MPT products in development are exclusively female-focused due to the readily available nature and regulatory precedent offered by female contraceptive active pharmaceutical ingredients (APIs); however, the opportunity to explore codevelopment with male contraceptive methods, which are at a comparatively early stage of development, should not be overlooked. These fields face parallel challenges including research and development, commercialization, regulatory approval, and market uptake, and these parallels can inform strategic alignment between the fields. One challenge that precludes codevelopment, however, is the path to market and associated funding models for these innovative, yet underappreciated fields. Without candid review, reconsideration, prioritization, and innovation led by the donor and investment communities, product developers will have no compelling reason to consider accepting the added regulatory and fiscal burden associated with combining development streams.

Turning the promise of multipurpose prevention technologies into a market reality: a commentary.

The promise of multipurpose prevention technologies (MPTs) for the prevention of HIV and unintended pregnancy are on the horizon. While many are still in clinical development, others are closer to becoming a realistic, accessible option for users, like the dual prevention pill (DPP). Researchers, governments, donors, and implementers will have to collaboratively address systemic challenges to successfully introduce and scale-up MPTs. To ensure the rollout of MPTs is successful, the global community should address user and country-specific needs, coordinate with advocates and policymakers, and set a realistic plan for product introduction and scale-up that considers the needs of both family planning (FP) and HIV programs, while laying the groundwork for future new product introduction. To achieve these aims, global and regional stakeholder coordination should emphasize country-led, person-centered decision-making while addressing: (1) procurement and supply chain barriers; (2) the potential burden on health systems; and (3) the impact on current programs.

Physicochemical considerations in the formulation development of silicone elastomer vaginal rings releasing 5-nitroimidazole drugs for the treatment of bacterial vaginosis.

Bacterial vaginosis (BV) is a common dysbiosis of the human vaginal microbiota characterized by depletion of hydrogen peroxide and lactic acid-producing Lactobacillus bacteria and an overgrowth of certain facultative anaerobic bacteria. Although short-term cure rates following treatment with frontline antibiotics (most notably oral metronidazole (MNZ), clindamycin vaginal cream, and MNZ vaginal gel) are generally high, longer-term recurrence rates are an issue. The development of vaginal formulations offering continuous/sustained administration of antibiotic drugs over one or more weeks might prove useful in reducing recurrence. Here, we report the manufacture and preclinical testing of matrix-type vaginal rings offering sustained release of four 5-nitroimidazole antimicrobial drugs either being used clinically or having potential in treatment of BV - MNZ, tinidazole (TNZ), secnidazole (SNZ) and ornidazole (ONZ). All four drugs showed good compatibility with a medical-grade addition-cure silicone elastomer based upon thermal analysis experiments, and matrix-type rings containing 250 mg (3.125 %w/w) of each drug were successfully manufactured by reaction injection molding. 28-day in vitro drug release studies demonstrated root-time kinetics, with daily release rates of 25, 22, 9 and 6 mg/day½ for SNZ, ONZ, MNZ and TNZ, respectively. The rank order of drug release from rings correlated with the simple molecular permeability parameter S/V, where S is the measured drug solubility in silicone fluid and V is the drug molecular volume. The relative merits of SNZ and ONZ over MNZ (the current reference treatment) are discussed. The data support development of vaginal rings for sustained release of 5-nitroimidazole compounds for treatment of BV.

Strategic actions to advance multipurpose prevention technologies in low- and middle-income countries.

Background: HIV, other sexually transmitted infections (STIs) and unintended pregnancies are critical and interlinked health risks for millions of women of reproductive age worldwide. Multipurpose prevention technologies (MPTs) offer an innovative approach for expanding combined pregnancy and/or disease prevention. So far, MPT development efforts have focused mostly on HIV prevention, but about half of product candidates comprise compounds active against non-HIV STIs as well. This review aims to provide a framework that promotes the efficient advancement of the most promising preclinical products through the development pathway and into the hands of end-users, with a focus on women in low- and middle-income countries (L/MICs). Methods: This mini review provides a summary of the current landscape of the MPT field. It comprises a landscape assessment of MPTs in development, complemented by a series of 28 in-depth, semi-structured key informant interviews (KIIs) with experts representing different L/MIC perspectives. Main results: We identified six primary action strategies to advance MPTs for L/MICs, including identification of key research gaps and priorities. For each action strategy, progress to date and key recommendations are included. Conclusions: To realize the life-saving potential of MPTs and maximize the momentum made to date, a strategic, collaborative and well-funded response to the gaps and next steps outlined in this paper is critical. A coordinated response can add rigor and efficiency to the development process, to successfully advance the most promising MPT products to the hands of end-users.

Experiences and attitudes towards Menstrual Suppression among Women with Bacterial vaginosis Randomised to Continuous Use of NuvaRing in Kenya.

Background: The contraceptive vaginal ring (NuvaRing), one of the Multipurpose Prevention Technologies (MPT) products, is effective in preventing unintended pregnancies and may contribute to reducing the frequency of Bacterial Vaginosis (BV), which is a risk factor for HIV acquisition, transmission, and shedding among women. NuvaRing may cause irregular menstruation, including menstrual suppression, which may influence women's decision on product choice, use, and acceptability. In this prospective cohort study, we assessed women's experiences with menstruation suppression following continued NuvaRing use. Methods: A total of 18 in-depth interviews were conducted using a semi-structured interview guide among purposively selected women with BV in Thika, Kenya, aged 18-40 years, who used NuvaRing continuously. All women received counseling on possibility of menstrual suppression following continuous NuvaRing use. Audio recordings were transcribed verbatim and thematically analyzed. Results: Participants who expected and were aware that menstrual suppression was a possible side effect of Nuvaring accepted its benefits, and expressed acceptance and desire to continue using NuvaRing. Participants who had not anticipated menstrual suppression expressed anxiety and fear, with some expressing desire to continue using NuvaRing but worried about unintended negative consequences. The ability to perform daily activities uninterrupted, reduced expenses on sanitary supplies, enhanced sexual pleasure and relationships, and absence of menstrual pain were benefits of menstrual suppression. Although all participants received counseling on menstrual suppression, some expressed anxiety over the possibility of unintended pregnancy. As a result, they frequented medical facilities for health check-ups and pregnancy tests, and some used combined oral contraceptives to induce menses. Conclusion: Understanding perceptions regarding menstrual suppression is crucial in offering targeted and comprehensive counseling to improve women's understanding of menstruation suppression to influence acceptance and use of NuvaRing. Additionally, improved male involvement in reproductive health concerns and women's autonomy in discussing reproductive health issues with partners is essential.

Synthesis of end-user research to inform future multipurpose prevention technologies in sub-Saharan Africa: a scoping review.

Introduction: Women in sub-Saharan Africa (SSA) experience disproportionately high rates of HIV infection and unintended pregnancy compared to their age-matched counterparts in other regions of the world. Multipurpose prevention technologies (MPTs) that offer protection against HIV and unintended pregnancy in a single product stand to address these dual sexual and reproductive health needs simultaneously. The aim of this scoping review is to identify factors that are important for optimizing the likelihood of MPT adoption by end users in SSA. Methods: Study inclusion criteria included MPT research (HIV and pregnancy prevention dual indication) published or presented in English from 2000 to 2022 and conducted in SSA amongst end-users (women aged 15-44), male partners, health care providers, and community stakeholders. References were identified by searching peer reviewed literature, grey literature, conference presentations (2015-2022), grant databases, and outreach to MPT subject matter experts. Of 115 references identified, 37 references met inclusion criteria and were extracted for analysis. A narrative synthesis approach was used to summarize findings within and across MPT products. Results: Studies were identified from six countries in SSA and a substantial proportion included a South African (n = 27) and/or Kenyan (n = 16) study site. Most studies utilized a qualitative study design (n = 22) and evaluated MPT acceptability and preferences by presenting hypothetical products through images or a list of product attributes (n = 21). The vaginal ring (n = 20), oral tablet (n = 20), and injection (n = 15) were examined most frequently. Across studies, there was high acceptability and demand for an HIV and pregnancy prevention MPT. End users valued choice in prevention product type as well as discreetness and long-acting options. Provider counseling and community sensitization were reported as essential for future introduction of novel MPT delivery forms. Conclusion: Recognizing the heterogeneity of women's preferences and changing reproductive and sexual health needs over the life course, choice is important in the delivery of pregnancy and HIV prevention products as well as amongst MPT products with distinct product profiles. End user research with active MPTs, vs. hypothetical or placebo MPTs, is necessary to advance understanding of end-user preferences and acceptability of future products.

Cost-effectiveness of the dual prevention pill for contraception and HIV pre-exposure prophylaxis.

Introduction: Women in sub-Saharan Africa (SSA) experience the world's highest rates of both HIV infection and unintended pregnancy. The Dual Prevention Pill (DPP) is a novel multipurpose prevention technology (MPT) that co-formulates HIV pre-exposure prophylaxis (PrEP) and combined hormonal oral contraception into a single daily pill. As a dual indication product, the DPP may be preferred by women facing these overlapping health risks. However, most SSA countries face severe healthcare resource constraints. Research is needed to assess whether, in what populations, and in what use cases the DPP would be cost-effective. Methods: We augmented an agent-based SSA HIV model with maternal health parameters including unintended pregnancy, abortion, and maternal mortality. Based on a previous market analysis, we assumed a primary DPP user population of current oral contraceptive users ages 25-49, and alternative user populations in different risk groups (age 15-24, sex workers, HIV-serodiscordant couples) and baseline product use profiles (unmet need for contraception, oral PrEP use, condom use). In three geographies (western Kenya, Zimbabwe, South Africa), we estimated HIV infections averted, pregnancies averted, disability-adjusted life-years (DALYs) averted, and the incremental cost-effectiveness ratio (ICER) over a 30-year time horizon, assuming equivalent adherence to the DPP as to oral contraceptives, higher adherence, or lower adherence. Results: The DPP is likely to be a cost-effective alternative to oral PrEP among users in need of contraception. Among women not already using PrEP, the DPP is likely to be cost-saving in sex workers and serodiscordant couples. The DPP is unlikely to be cost-effective in oral contraceptive users in the general population. Switching from oral contraception to the DPP could be net harmful in some settings and populations if it were to substantially reduces adherence to oral contraception. Results were robust to a range of time horizons or discount rates. Conclusion: The DPP has the potential to be cost-effective and cost-saving in populations at substantial HIV risk. Outcomes are sensitive to adherence, implying that effective counseling and decision-making tools for users considering the DPP will be essential. More research is needed to understand real-life adherence patterns and ensure health benefits achieved from contraception alone are not lost.

Co-delivery of an HIV prophylactic and contraceptive using PGSU as a long-acting multipurpose prevention technology.

OBJECTIVES: Poly(glycerol sebacate) urethane (PGSU) elastomers formulated with 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), levonorgestrel (LNG), or a combination thereof can function as multipurpose prevention technology implants for prophylaxis against HIV and unintended pregnancies. For these public health challenges, long-acting drug delivery technologies may improve patient experience and adherence. Traditional polymers encounter challenges delivering multiple drugs with dissimilar physiochemical properties. PGSU offers an alternative option that successfully delivers hydrophilic EFdA alongside hydrophobic LNG. METHODS: This article presents the formulation, design, and characterization of PGSU implants, highlighting the impact of API loading, dimensions, and individual- versus combination-loading on release rates. RESULTS: Co-delivery of hydrophilic EFdA alongside hydrophobic LNG acted as a porogen to accelerate LNG release. Increasing the surface area of LNG-only implants increased LNG release. All EFdA-LNG, EFdA-only, and LNG-only formulated implants demonstrated low burst release and linear release kinetics over 245 or 122 days studied to date. CONCLUSION: PGSU co-delivers two APIs for HIV prevention and contraception at therapeutically relevant concentrations in vitro from a single bioresorbable, elastomeric implant. A new long-acting polymer technology, PGSU demonstrates linear-release kinetics, dual delivery of APIs with disparate physiochemical properties, and biocompatibility through long-term subcutaneous implantation. PGSU can potentially meet the demands of complex MPT or fixed-dose combination products, where better solutions can serve and empower patients.

Attitudes Toward Menstrual Suppression Among Cyclic and Continuous Contraceptive Vaginal Ring Users in Kenya.

Objective: Multipurpose prevention technologies (MPTs) are developmental dual-purpose options that would provide women with a contraceptive as well as a prevention modality aimed at sexually transmitted infections. The contraceptive vaginal ring (CVR) has many properties that makes it an ideal MPT candidate. The objective of this study is to understand women's attitudes towards menstrual suppression, a potential side effect of using a CVR, and how to address these attitudes for MPT vaginal rings in development. Materials and methods: We analyzed data derived from a subset of cohort study participants (n=45) in Thika, Kenya between January 2016- December 2018. The primary study enrolled 121 women 18-40 years with bacterial vaginosis and randomized them to cyclic or continuous CVR use for eight months. During the 6-month follow-up, a questionnaire eliciting attitudes towards menstrual suppression was administered. Responses to the menstrual suppression questionnaire between participants in the cyclic and continuous CVR use groups were compared. Likert-scale responses were summed to create a menstrual suppression attitude summary score, and a hierarchical cluster analysis was conducted to identify similarities in response patterns among all participants. Results: Totally 81.8% of continuous CVR users believed that one was less likely to get pregnant after using hormonal medication to suppress menses, compared to 47.8% of cyclic CVR users (P=0.02), and were more worried it would cause long-term health effects (86.4% vs 60.9%, p = 0.05). The menstrual suppression attitude summary score ranged from 8 to 42, with lower scores indicating negative attitudes. The summary score identified three distinct clusters. When asked if menstrual suppression effects long-term health; 100% of Cluster 3 was worried compared to 80.8% of Cluster 2 and 46.2% of Cluster 1 (p = 0.03). The average summary score among Cluster 3 (Mean = 14.8, SD = 4.6) was lower (p < 0.001) and women were more worried about discomfort during sex (p=0.05) as well as their sexual partners feeling the ring (p=0.02). Conclusion: Women are more likely to have negative attitudes if they believe menstrual suppression hinders future reproductive health. Education on cycle control and fertility could mitigate negative attitudes and improve uptake of CVRs.

Making the Case for Joint Decision-Making in Future Multipurpose Prevention Technology (MPT) Choice: Qualitative Findings on MPT Attribute Preferences from the CUPID Study (MTN-045).

INTRODUCTION: Young women in sub-Saharan Africa account for two-thirds of all new HIV infections and face high rates of unintended pregnancy. Multipurpose prevention technologies (MPTs) are promising products under development that are designed to simultaneously prevent HIV and unintended pregnancy. Since MPTs will be used in the context of sexual relationships, ensuring acceptability and use requires understanding the role of male partners in MPT use decision-making. METHODS: This paper draws on qualitative data from 39 couples enrolled in the Microbicide Trials Network (MTN) 045 study, conducted in 2019-2020. Partners completed a discrete choice experiment (DCE), first separately and then jointly, to measure preferences for future MPT attributes and then completed a qualitative interview. We also draw on quantitative data from interviewer observation about who dominated the decision-making process during the joint DCE. Content analysis was used to examine (1) how couples made decisions on existing non-MPT HIV and pregnancy prevention products; (2) how couples made decisions on future ideal-MPT product during the DCE; and (3) how these decision-making processes varied by decision-making dominance (10 male, 10 female and 19 equal) and interview type (19 joint and 20 separate). RESULTS: Existing non-MPT product decisions focused on trust between partners and product attributes, while future ideal-MPT product decisions exclusively focused on product attributes. Across existing and future products, preferences for product attributes varied by gender. Male partners were most concerned with limiting side effects impacting sexual pleasure, female partners were most concerned with limiting side effects causing physical symptoms and both were concerned with the return to fertility. Across all dominance and interview types, couples reported making decisions together and female partners were often able to negotiate with male partners for their preferred product or set of product attributes. CONCLUSIONS: Research activities in this study provided an opportunity for couples to openly present their product attribute preferences to their partner, learn about their partner's attribute preferences, negotiate for their ideal set of attributes and ultimately choose attributes that benefited the couple without disempowering the female partner. Future research should focus on the utility of couple-based decision-making aids or similar tools for facilitating joint MPT decision-making.

U.S. Women Need the Dapivirine Ring, Too: FDA as Structural Barrier to HIV Prevention for Women.

The dapivirine monthly vaginal ring-a discreet, anti-HIV microbicide created specifically for women-has received a positive scientific opinion by the European Medicines Agency and is included in the WHO HIV prevention guidelines. It has received regulatory approvals in several countries in southern and eastern Africa. During the review of the New Drug Application that was submitted in December 2020, FDA advised the developer, International Partnership for Microbicides, that it was unlikely to be approved in the United States; the application has since been withdrawn. This commentary will present the case for FDA approval for the dapivirine ring. Advocacy is urgently needed to protect U.S. women's access to user-controlled HIV prevention technologies, consistent with both global regulatory decisions to date and with a reproductive justice framework. Women continue to need the fullest range of HIV prevention methods to integrate into their lives in the most practical and effective way possible.

Long-acting biodegradable implant for sustained delivery of antiretrovirals (ARVs) and hormones.

Women worldwide confront two major reproductive health challenges: the need for contraception and protection from sexually transmitted infections, including Human Immunodeficiency Virus (HIV). Multipurpose Prevention Technologies (MPTs) that simultaneously prevent unintended pregnancy and HIV could address these challenges with a single product. Here, we developed a long-acting (LA) subcutaneously administered and biodegradable implant system that provides sustained delivery of contraceptive and antiretroviral (ARV) with zero-order release kinetics. The MPT system involves two implants comprising an extruded tube of a biodegradable polymer, poly(ε-caprolactone) (PCL). Each implant is filled with a formulation of progestin [levonorgestrel (LNG) or etonogestrel (ENG)], or a formulation of a potent ARV [tenofovir alafenamide (TAF), or 4'-Ethynyl-2-fluoro-2'-deoxyadenosine (EFdA)]. We demonstrated sustained in-vitro release of LNG, ENG, and EFdA from the implant system for 13-17 months, while maintaining high stability of the drugs (>99%) within the implant reservoirs. We further elucidated the controlled release mechanism of the implant and leveraged several tunable parameters (e.g., type and quantity of the excipient, PCL properties, and implant wall thickness) to tailor the release kinetics and enhance the mechanical integrity of the MPT implant. The optimized MPT showed sustained in-vitro release of ENG and EFdA over 1 year while maintaining a high level of formulation stability and structural integrity. The MPT implant system was further evaluated in a preclinical study using a rodent model and demonstrated sustained release of EFdA (6 months) and ENG (12 months) with high stability of the drug formulation (>95%). This manuscript supports the continued advancement of LA delivery systems for MPTs.

Multipurpose Prevention Technologies: Oral, Parenteral, and Vaginal Dosage Forms for Prevention of HIV/STIs and Unplanned Pregnancy.

There is a high global prevalence of HIV, sexually transmitted infections (STIs), and unplanned pregnancies. Current preventative daily oral dosing regimens can be ineffective due to low patient adherence. Sustained release delivery systems in conjunction with multipurpose prevention technologies (MPTs) can reduce high rates of HIV/STIs and unplanned pregnancies in an all-in-one efficacious, acceptable, and easily accessible technology to allow for prolonged release of antivirals and contraceptives. The concept and development of MPTs have greatly progressed over the past decade and demonstrate efficacious technologies that are user-accepted with potentially high adherence. This review gives a comprehensive overview of the latest oral, parenteral, and vaginally delivered MPTs in development as well as drug delivery formulations with the potential to advance as an MPT, and implementation studies regarding MPT user acceptability and adherence. Furthermore, there is a focus on MPT intravaginal rings emphasizing injection molding and hot-melt extrusion manufacturing limitations and emerging fabrication advancements. Lastly, formulation development considerations and limitations are discussed, such as nonhormonal contraceptive considerations, challenges with achieving a stable coformulation of multiple drugs, achieving sustained and controlled drug release, limiting drug-drug interactions, and advancing past preclinical development stages. Despite the challenges in the MPT landscape, these technologies demonstrate the potential to bridge gaps in preventative sexual and reproductive health care.

Giving voice to the end-user: input on multipurpose prevention technologies from the perspectives of young women in Kenya and South Africa.

ABSTRACTUnintended pregnancy and unmet need for modern contraception contribute substantially to reproductive health disparities globally. In sub-Saharan Africa they occur in contexts of disproportionately high rates of HIV infection. Multipurpose prevention technologies (MPTs) can address HIV and pregnancy prevention needs in a single "2-in-1" product; however, few studies have solicited end-user views to inform design of new MPTs. We conducted the Tablets, Ring, Injections as Options (TRIO) study with young women aged 18-30 in Kenya and South Africa (N = 277) to examine preferences and acceptability of future MPTs. In a randomised clinical cross-over study in which women used three placebo delivery forms, we complemented quantitative acceptability assessments with in-depth interviews and focus group discussions (N = 88 participants). We examined anticipated enablers and barriers to adoption and use of future MPTs and synthesised novel product design recommendations. Participants expressed high interest in MPTs. Anticipated side effects constituted a primary concern; however, many expected barriers were not dosage form-specific, but addressed contextual factors instead, such as fears regarding use of new biomedical technologies, misunderstandings and stigma regarding use, and navigating partner disclosure and engagement. Women preferred MPTs that offered discreetness and long-duration protection to minimise user-burden, did not interfere with their relationships, and conferred protection for unanticipated situations. End-user research to identify and pre-emptively address potential barriers while underscoring benefits to a new MPT product is vital. Attention to cultural contexts in implementation of new MPTs is important to communicating perceived benefits, achieving acceptability and maximising public health benefits.