A Scoping Review of Oral Pre-exposure Prophylaxis for Cisgender and Transgender Adolescent Girls and Young Women: What Works and Where Do We Go from Here?

Adolescent girls and young women (AGYW) are disproportionately affected by HIV, and oral pre-exposure prophylaxis (PrEP) can reduce HIV acquisition. The purpose of this scoping review was to synthesize results from interventions along the PrEP continuum for AGYW to inform research and programs. We searched electronic databases for studies published between January 2012-July 2021 and conducted secondary reference searching. Studies were included if they assessed interventions to increase PrEP interest, uptake, or continuation among AGYW. Results were synthesized narratively. Of 2168 citations identified, 50 studies were eligible for inclusion, and 20 contained AGYW-specific data. Among cisgender and transgender AGYW, studies overall demonstrated a positive impact on PrEP interest and uptake but generally attained suboptimal continuation rates. Results demonstrate feasibility of deploying PrEP across diverse settings-particularly when interventions are layered, tailored to AGYW, and include differentiated delivery-but also highlight knowledge gaps and the need for more holistic metrics of success.

RESUMEN: Las adolescentes y las mujeres jóvenes se ven afectadas de forma desproporcionada por el VIH, y la Profilaxis Pre-Exposición oral (PrEP) puede reducir la adquisición del VIH. El propósito de esta revisión de alcance fue sintetizar los resultados de las intervenciones a lo largo del continuo de la PrEP para las adolescentes y las mujeres jóvenes con el fin de informar la investigación y los programas. Se realizaron búsquedas en bases de datos electrónicas de estudios publicados entre enero 2012 a julio 2021 y se llevó a cabo una búsqueda secundaria de referencias. Los estudios se incluyeron si evaluaban intervenciones para aumentar el interés, la iniciación, o la continuación de la PrEP entre las adolescentes y las mujeres jóvenes. Los resultados se sintetizaron narrativamente. De las 2168 citas identificadas, 50 estudios fueron elegibles para inclusión y 20 contenían datos específicos de las adolescentes y las mujeres jóvenes. Entre las adolescentes y las mujeres jóvenes cisgénero y transgénero, los estudios demostraron un impacto positivo en el interés y la iniciación de la PrEP, pero en general alcanzaron tasas de continuación subóptimas. Los resultados demuestran la viabilidad del despliegue de la PrEP en diversos entornos­en particular cuando las intervenciones son estratificadas, se adaptan a las adolescentes y las mujeres jóvenes, e incluyen una prestación diferenciada­pero también destacan las lagunas de conocimiento y la necesidad de una métrica más holística del éxito.

Early implementation learnings on acceptability and feasibility of "V": a multi-level PrEP intervention designed with and for adolescent girls and young women in Zimbabwe.

INTRODUCTION: Adolescent girls and young women (AGYW) remain disproportionately affected by HIV in Zimbabwe. Several HIV prevention options are available, including oral tenofovir-based pre-exposure prophylaxis (PrEP), however AGYW face unique barriers to PrEP uptake and continuation and novel approaches are therefore needed to empower AGYW to use PrEP. The objective of this study was to characterize early learnings from implementing a multi-level intervention consisting of fashionable branding (including a "V Starter Kit"), service integration, and peer education and support throughout a young woman's journey using oral PrEP across four phases of implementation, from creating demand, preparing for PrEP, initiation of PrEP, and adherence to PrEP. METHODS: A mixed methods implementation research study was undertaken, including site observations and interviews to explore the acceptability of "V" and its relevance to target users, as well as the feasibility of integrating "V" with existing service delivery models. Interviews (n = 46) were conducted with healthcare workers, Brand Ambassadors, and young women purposively sampled from four implementation sites. Interview data was analyzed thematically using the framework method for qualitative data management and analysis. Project budgets and invoices were used to compile unit cost and procurement data for all "V" materials. RESULTS: "V" was acceptable to providers and young women due to attractive branding coupled with factual and thought-provoking messaging, establishing "a girl code" for discussing PrEP, and addressing a gap in communications materials. "V" was also feasible to integrate into routine service provision and outreach, alongside other services targeting AGYW. Cost for the "V" branded materials ranked most essential-FAQ insert, pill case, makeup bag, reminder sticker-were $7.61 per AGYW initiated on PrEP. CONCLUSION: "V" is a novel approach that is an acceptable and feasible multi-level intervention to improve PrEP access, uptake, and continuation among AGYW, which works through empowering AGYW to take control of their HIV prevention needs. In considering "V" for scale up in Zimbabwe, higher volume procurement and a customized lighter package of "V" materials, while still retaining V's core approach, should be explored.

Feasibility and economic costs of syphilis self-testing to expand test uptake among gay, bisexual and transgender men: results from a randomised controlled trial in Zimbabwe.

BACKGROUND: Access to syphilis testing and treatment is frequently limited for men who have sex with men (MSM). A two-armed randomised controlled trial compared feasibility and costs of facility-based syphilis testing with self-testing among MSM in Zimbabwe. METHODS: This randomised controlled trial was conducted in Harare, with participants randomised 1:1. Syphilis self-testing was offered in community-based settings. The primary outcome was the relative proportion of individuals taking up testing. Total incremental economic provider and user costs, and cost per client tested, diagnosed and treated were assessed using ingredients-based costing in 2020US$. RESULTS: A total of 100 men were enrolled. The two groups were similar in demographics. The mean age was 26years. Overall, 58% (29/50) and 74% (37/50) of facility- and self-testing arm participants, respectively, completed syphilis testing. A total of 28% of facility arm participants had a reactive test, with 50% of them returning for confirmatory testing yielding 28% reactivity. In the self-testing arm, 67% returned for confirmatory testing, with a reactivity of 16%. Total provider costs were US$859 and US$736, and cost per test US$30 and US$15 for respective arms. Cost per reactive test was US$107 and US$123, and per client treated US$215 and US$184, respectively. The syphilis test kit was the largest cost component. Total user cost per client per visit was US$9. CONCLUSION: Syphilis self-testing may increase test uptake among MSM in Zimbabwe. However, some barriers limit uptake including lack of self-testing and poor service access. Bringing syphilis testing services to communities, simplifying service delivery and increasing self-testing access through community-based organisations are useful strategies to promote health-seeking behaviours among MSM.

Syphilis self-testing to expand test uptake among men who have sex with men: a theoretically informed mixed methods study in Zimbabwe.

OBJECTIVES: Self-testing for STIs such as HIV and syphilis may empower sexual minorities and expand uptake of STI testing. While much is known about HIV self-testing (HIVST), less is known about syphilis self-testing, particularly in low-income settings. The objective of this study is to determine context-specific facilitators and barriers for self-testing and to assess the usability of syphilis self-testing in Zimbabwe among men who have sex with men (MSM). METHODS: This mixed methods study was conducted in Harare as part of a larger syphilis self-testing trial. The study included in-depth interviews (phase I) followed by usability testing and a second interview (phase II). In-depth interviews were conducted with MSM and key informants prior to syphilis self-testing. The same MSM then used the syphilis self-test, quantitatively assessed its usability and participated in a second in-depth interview. Phase I data were analysed using a thematic approach, guided by an adapted social ecological model conceptual framework. Phase II interviews were analysed using rapid assessment procedure methodology, and usability was assessed using a pre-established index, adapted from existing HIVST scales. RESULTS: Twenty MSM and 10 key informants were recruited for phase I in-depth interviews, and 16 of these MSM participated in phase II by completing a syphilis self-test kit. Facilitating factors for self-testing included the potential for increased privacy, convenience, autonomy, and avoidance of social and healthcare provider stigma. Barriers included the fear to test and uncertainty about linkage to care and treatment. Data from the Usability Index suggested high usability (89.6% on a 0-100 scale) among the men who received the self-test. CONCLUSIONS: MSM in Zimbabwe were willing to use syphilis self-test kits and many of the barriers and facilitators were similar to those observed for HIVST. Syphilis self-testing may increase syphilis test uptake among sexual minorities in Zimbabwe and other low-income and middle-income countries.

Efficiency in PrEP Delivery: Estimating the Annual Costs of Oral PrEP in Zimbabwe.

Although oral PrEP is highly effective at preventing HIV acquisition, optimizing continuation among beneficiaries is challenging in many settings. We estimated the costs of delivering oral PrEP to populations at risk of HIV in seven clinics in Zimbabwe. Full annual economic costs of oral PrEP initiations and continuation visits were estimated from the providers' perspective for a six-clinic NGO network and one government SGBV clinic in Zimbabwe (January-December 2018). Disaggregating costs of full initiation and incremental follow-up visits enabled modeling of the impact of duration of continuation on the cost per person-year ($pPY) on PrEP. 4677 people initiated oral PrEP, averaging 2.7 follow-up visits per person. Average cost per person initiated was $238 ($183-$302 across the NGO clinics; $86 in the government facility). The full cost per initiation visit, including central and direct costs, was $178, and the incremental cost per follow-up visit, capturing only additional resources used directly in the follow up visits, was $22. The average duration of continuation was 3.0 months, generating an average $pPY of $943, ranging from $839 among adolescent girls and young women to $1219 in men. Oral PrEP delivery costs varied substantially by scale of initiations and by duration of continuation and type of clinic. Extending the average oral PrEP continuation from 2.7 to 5 visits (about 6 months) would greatly improve service efficiency, cutting the $pPY by more than half.

Engaging HIV-prevention ambassadors to promote oral PrEP among adolescent girls and young women: results of a Zimbabwe field test.

The HIV Prevention Ambassador Training Package for Adolescent Girls and Young Women was created in collaboration with adolescent girls and young women (AGYW) to improve skills, knowledge, and attitudes about oral pre-exposure prophylaxis (PrEP) among peer "ambassadors". It was field tested with 17 ambassadors in Mazowe District, Zimbabwe and changes in ambassadors' knowledge and attitudes about oral PrEP, as well as changes in oral PrEP uptake among AGYW in the district, were assessed. The training package improved oral PrEP knowledge among trained ambassadors and built AGYW's skills to advocate for oral PrEP awareness and rollout. Use of the training package correlated with a 59% increase in oral PrEP uptake among AGYW in Mazowe District in the seven months following the training. The ambassador training package could help support oral PrEP introduction and scale up in countries with high HIV incidence by engaging AGYW in oral PrEP rollout in their communities.

Health care providers' attitudes toward and experiences delivering oral PrEP to adolescent girls and young women in Kenya, South Africa, and Zimbabwe.

BACKGROUND: In Kenya, South Africa, and Zimbabwe, oral pre-exposure prophylaxis (PrEP) is recommended for adolescent girls and young women (AGYW) at high risk of HIV. Health providers play a critical role in the uptake and effective use of sexual and reproductive health services; however, few published studies have explored providers' attitudes toward and experiences delivering PrEP to AGYW. METHODS: We conducted a cross-sectional qualitative study, interviewing 113 providers at 36 public, private, and nongovernmental health facilities in Kenya, South Africa, and Zimbabwe that were offering PrEP during the research period or were likely to offer PrEP in the future. Data were coded in NVivo 11, and an applied thematic analysis was conducted. RESULTS: Most providers preferred that adolescent girls wait until age 18 to have sex but acknowledged that many girls younger than 18 could benefit from oral PrEP. Their primary concern was whether adolescent girls would be able to take PrEP daily, especially if they do not tell their parents or partners they are using it. Providers reported that it was more challenging to deliver PrEP and other HIV services to girls younger than 18. Those with experience providing PrEP pointed to stigma and lack of PrEP awareness in communities as two primary barriers to PrEP uptake and use. CONCLUSIONS: Providers were generally accepting of oral PrEP as an HIV prevention option for AGYW; however, many had negative attitudes about adolescent girls being sexually active and concerns about whether they could take PrEP daily. Results were used to update national PrEP training materials to address negative provider attitudes about PrEP use by AGYW.

Defining principles for a choice-based approach to HIV prevention.

The HIV prevention landscape is on the cusp of an unprecedented era of multiple biomedical prevention products available for distribution. Several HIV prevention options, such as oral pre-exposure prophylaxis (PrEP), dapivirine vaginal rings, and injectable cabotegravir for PrEP, are becoming more widely available. Although the future HIV prevention market promises to be rich in options, it would benefit from a core set of principles that uphold choice in all phases of product development, assessment, and introduction. These principles, as presented in this Viewpoint, show the applicability, opportunities, and challenges of choice in different contexts of HIV prevention and provide checkpoints of accountability. By committing to these principles, stakeholders at national and global levels can advance choice across all phases of the HIV prevention market, thereby ensuring that individuals can realise their right to choose when and how to prevent HIV in their own lives.

Factors motivating female sex workers to initiate pre- exposure prophylaxis for HIV prevention in Zimbabwe.

BACKGROUND: Female sex workers (FSWs) have a 26 times greater chance of HIV infection compared to the women in the general population. The World Health Organization recommends pre-exposure prophylaxis (PrEP) for population groups with an HIV incidence of 3% or higher and FSWs in southern Africa fit this criteria. This study sought to understand factors that motivate FSWs to initiate PrEP, in Harare, Zimbabwe. METHODS: We purposively selected and recruited 20 FSWs to participate in the study in-order to gain an in-depth understanding of factors that motivate FSWs to initiate PrEP in Harare, Zimbabwe. We identified FSW who had been initiated on PrEP at a specialized clinic providing comprehensive sexual reproductive health (SRH) services for sex workers including HIV prevention options. We used a descriptive phenomenological approach to collect and analyze the data. Data was analyzed using Colaizzi's seven steps to analyze data. FINDINGS: Two broad themes were identified as intrinsic and extrinsic motivators. The two broad themes each have several sub-themes. The sub-themes under intrinsic motivation were (i) Self- protection from HIV infection and (ii) condoms bursting. Six sub-themes were identified as external motivators for initiating PrEP, these included (i) occupational risk associated with sex work, (ii) increased chance of offering unprotected sex as a motivator to initiate PrEP, (iii) positive encouragement from others (iv) need to take care of the children and (v) prior participation in HIV prevention research studies and (vi) Gender Based Violence. CONCLUSIONS: Understanding the factors that motivate FSWs to initiate PrEP is critical in developing contextually appropriate strategies to promote PrEP initiation and adherence strategies within specific and eligible populations for receiving PrEP according to the WHO guidelines (2015).

Test and Prevent: Evaluation of a Pilot Program Linking Clients With Negative HIV Test Results to Pre-exposure Prophylaxis in Zimbabwe.

BACKGROUND: As HIV testing increases worldwide, programs are reaching individuals without HIV infection who are at risk of exposure and may be candidates for oral pre-exposure prophylaxis (PrEP). Although linkage of individuals with HIV infection to treatment is a global priority (referred to as "test and treat"), less attention is given to individuals with negative HIV test results. We developed the "Test and Prevent" pilot program to intentionally link at-risk clients with negative HIV test results to PrEP services. The intervention included risk assessment of all clients with a negative result from HIV testing (with national risk assessment tool), accompanied referral, fast-tracking, and targeting follow-up. METHODS: The intervention was conducted in Bulawayo, Zimbabwe, at 6 public sector sites from October 2019 to February 2020. We collected routine monitoring data from all study sites and tracked referral completion and PrEP initiation among clients who enrolled. We conducted in-depth interviews with providers (n=12), facility managers (n=5), and female clients (n=17) to explore acceptability. RESULTS: Among clients referred for PrEP (n=206), 98% completed their referrals and started PrEP. However, only 3% of clients who received a negative test result during the study period were referred. Low referrals stemmed from lack of screening (39% of clients with negative HIV test results were not screened) and lack of eligibility among clients who were screened (only 6% of those screened qualified as candidates for PrEP per the national screening tool). Qualitative results indicate that some providers purposefully did not complete screening with clients they felt were not at risk and that workload could have contributed to low screening uptake.Qualitative interviews showed that Test and Prevent was acceptable among both providers and clients. Clients were happy to learn about PrEP following HIV testing, and the additional support of accompanied referrals and fast-tracking encouraged them to access PrEP and made them feel valued. Providers were burdened by workload constraints but felt that Test and Prevent was important and should be scaled to other sites. CONCLUSION: Intentionally linking clients with negative results to PrEP immediately following HIV testing was found to be acceptable from both provider and client perspectives, yet screening procedures need closer examination and reinforcement for the program to realize a larger impact.

The SHAZ! project: results from a pilot randomized trial of a structural intervention to prevent HIV among adolescent women in Zimbabwe.

UNLABELLED: Adolescent females in Zimbabwe are at high risk for HIV acquisition. Shaping the Health of Adolescents in Zimbabwe (SHAZ!) was a randomized controlled trial of a combined intervention package including life-skills and health education, vocational training, micro-grants and social supports compared to life-skills and health education alone. SHAZ! was originally envisioned as a larger effectiveness trial, however, the intervention was scaled back due to contextual and economic conditions in the country at the time. SHAZ! enrolled 315 participants randomly assigned to study arm within blocks of 50 participants (158 intervention and 157 control). The intervention arm participants showed statistically significant differences from the control arm participants for several outcomes during the two years of follow up including; reduced food insecurity [IOR = 0.83 vs. COR = 0.68, p-0.02], and having their own income [IOR = 2.05 vs. COR = 1.67, p = 0.02]. Additionally, within the Intervention arm there was a lower risk of transactional sex [IOR = 0.64, 95% CI (0.50, 0.83)], and a higher likelihood of using a condom with their current partner [IOR = 1.79, 95% CI (1.23, 2.62)] over time compared to baseline. There was also evidence of fewer unintended pregnancies among intervention participants [HR = 0.61, 95% CI (0.37, 1.01)], although this relationship achieved only marginal statistical significance. Several important challenges in this study included the coordination with vocational training programs, the political and economic instability of the area at the time of the study, and the difficulty in creating a true standard of care control arm. Overall the results of the SHAZ! study suggest important potential for HIV prevention intervention packages that include vocational training and micro-grants, and lessons for further economic livelihoods interventions with adolescent females. Further work is needed to refine the intervention model, and test the impact of the intervention at scale on biological outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT02034214.