PrEP Method Switching: Will it Yield Greater Coverage of HIV Protection? Applying Lessons Learned from Family Planning to Guide Future Research in the Context of PrEP Choice.

PURPOSE OF REVIEW: Despite the growing availability of oral PrEP, coverage remains suboptimal. Through the introduction of additional PrEP methods, including vaginal rings and long-acting injectable formulations, health systems globally are on the cusp of offering PrEP methods that vary by route of administration, efficacy, and frequency of use. With PrEP choice, it will be important to explore PrEP use patterns to better understand how the ability to choose and switch products affects coverage and continuation. In this review, we draw parallels with family planning (FP) by summarizing how method choice and product switching affected contraceptive coverage globally, synthesize what is known about PrEP product switching, and outline evidence gaps to help guide future research on PrEP switching in the context of choice. RECENT FINDINGS: Decades of research in FP has demonstrated that product switching is common and can lead to more satisfaction and increases in contraceptive use. While research on PrEP product switching is nascent, findings suggest switching is common, and that providing more than one PrEP option can increase coverage. Key evidence gaps include understanding product switching in the context of full versus constrained choice, switching in the context of temporary need, and developing interventions that promote product switching for those who could benefit. Providing choice and allowing people to start, stop, and switch products according to their needs and desires is a core component of a rights-based approach to HIV prevention. More research is needed to better understand what drives use patterns, including switching, and how to leverage choice to improve coverage. Standard definitions -some of which have been proposed in this review-are needed to inform comparable measurement. Finally, there is a need to holistically frame PrEP use to acknowledge changes in need over the life course, thus making method switching a standard part of HIV prevention.

Acceptability of the dapivirine vaginal ring for HIV-1 prevention among women reporting engagement in transactional sex.

We assessed if acceptability of the dapivirine vaginal ring for HIV prevention differed among the subgroup of women who reported engaging in transactional sex prior to enrollment in MTN-020/ASPIRE (phase III trial in Malawi, South Africa, Uganda, and Zimbabwe, 2012-2015; n = 2629). Transactional sex was defined as receipt of money, goods, gifts, drugs, or shelter in exchange for sex in the past year. Dimensions of acceptability included: ease of use and physical sensation in situ, impacts on sex, partner's opinion, and likelihood of future use. We used Poisson regression models with robust standard errors to compare risk of acceptability challenges by baseline history of transactional sex. At product discontinuation, women exchanging sex found the ring comfortable (90%), easy to insert (92%) and nearly all (96%) were likely to use the ring in the future. Women who had exchanged sex were more likely to report feeling the ring during sex (ARR 1.43, 95% CI: 1.09, 1.89; p = 0.01) and slightly more likely to mind wearing the ring during menses (ARR 1.22, 95% CI: 1.01, 1,46; p = 0.04) and during sex (ARR 1.22, 95% CI: 1.02, 1.45; p = 0.03). Messaging and counseling should include enhanced support for use during sex and menses to support optimal use.

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.

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.

The case for prevention - Primary HIV prevention in the era of universal test and treat: A mathematical modeling study.

Background: As antiretroviral therapy (ART) has scaled up and HIV incidence has declined, some have questioned the continued utility of HIV prevention. This study examines the role and cost-effectiveness of HIV prevention in the context of "universal test and treat" (UTT) in three sub-Saharan countries with generalized HIV epidemics. Methods: Scenarios were created in Spectrum/Goals models for Lesotho, Mozambique, and Uganda with various combinations of voluntary medical male circumcision (VMMC); pre-exposure prophylaxis; and a highly effective, durable, hypothetical vaccine layered onto three different ART scenarios. One ART scenario held coverage constant at 2008 levels to replicate prevention modeling studies that were conducted prior to UTT. One scenario assumed scale-up to the UNAIDS treatment goals of 90-90-90 by 2025 and 95-95-95 by 2030. An intermediate scenario held ART constant at 2019 coverage. HIV incidence was visualized over time, and cost per HIV infection averted was assessed over 5-, 15-, and 30-year time frames, with 3% annual discounting. Findings: Each prevention intervention reduced HIV incidence beyond what was achieved by ART scale-up alone to the 90-90-90/95-95-95 goals, with near-zero incidence achievable by combinations of interventions covering all segments of the population. Cost-effectiveness of HIV prevention may decrease as HIV incidence decreases, but one-time interventions like VMMC and a durable vaccine may remain cost-effective and even cost-saving as ART is scaled up. Interpretation: Primary HIV prevention is still needed in the era of UTT. Combination prevention is more impactful than a single, highly effective intervention. Broad population coverage of primary prevention, regardless of cost-effectiveness, will be required in generalized epidemic countries to eradicate HIV.

Vaginal ring acceptability: A systematic review and meta-analysis of vaginal ring experiences from around the world.

OBJECTIVE: The vaginal ring (ring) is a female-initiated, long-acting drug delivery system for different indications, including HIV prevention. Our aim was to provide evidence for acceptability of the vaginal ring across indications to support dapivirine and multipurpose prevention technology ring introduction and roll out. STUDY DESIGN: This systematic review and meta-analysis followed PRISMA guidelines. We searched PubMed, Web of Science, Embase, and grey literature for publications reporting favorable ring acceptability and secondary outcomes involving actual ring use (comfort, ease of ring use, ring comfort during sex, expulsions, and vaginal symptoms) or hypothetical acceptability for any indication published January 1, 1970-June 15, 2021. We estimated random-effects pooled prevalence, assessing between-study variation using meta-regression. RESULTS: Of 2,234 records, we included 123 studies with 40,434 actual and hypothetical ring users. The primary outcome assessment included 50 studies with 60 ring subgroups totaling 19,271 ring users. The favorable acceptability pooled prevalence was 85.6% (95%CI 81.3, 89.0), while hypothetical acceptability among non-ring users was 27.6% (95%CI 17.5, 40.5). In meta-regression, acceptability was higher in menopause (95.4%; 95%CI 88.4, 98.2) compared to contraceptive rings (83.7%; 95%CI 75.6, 89.5). Acceptability was lower in pharmacokinetic studies (50%; 95%CI 22.1, 77.9) compared to RCTs (89.5%; 95%CI 85.8.92.4) and in studies assessing acceptability at ≥12 months (78.5%; 95%CI 66.5, 87.1) versus studies assessing acceptability at <3 months (91.9%; 95%CI 83.7, 96.1). European (90.6%; 95%CI 83.9, 94.7), Asian (97.1%; 95%CI 92.0, 99.0), and multi-region studies (93.5%; 95%CI 84.6, 97.4) reported more favorable acceptability compared to African studies (59.4%; 95%CI 38.3, 77.5). Secondary outcomes were similarly favorable, including ring comfort (92.9%; 95%CI 89.2, 95.4), ease of use (90.9%; 95%CI 86.5, 94.0), and comfort during sex (82.7%; 95%CI 76.4, 87.6). Limitations include inconsistent outcome definitions and unmeasured factors affecting acceptability. CONCLUSIONS: Women who used vaginal rings reported they were acceptable across indications geographic regions and indications. Policy makers should consider the ring as an important option for pregnancy and HIV prevention drug development. IMPLICATIONS: This review found favorable acceptability among vaginal ring users across indications and geographic areas, in contrast to low hypothetical acceptability among non-users. Vaginal rings are an important drug delivery system for pregnancy and HIV preventions, and scale-up should plan to address initial hesitancy among new users.

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.

Introducing the Dapivirine Vaginal Ring in Sub-Saharan Africa: What Can We Learn from Oral PrEP?

PURPOSE OF REVIEW: Clinical trials have found that the dapivirine vaginal ring (DVR) is safe to use and effective at reducing women's risk of acquiring HIV infection. As countries prepare for the introduction of this novel long-acting, woman-controlled prevention method, an examination of key learnings from oral pre-exposure prophylaxis (PrEP) delivery will help programs leverage successful innovations and approaches to support DVR scale-up and expand the method mix for HIV prevention. RECENT FINDINGS: Intensive efforts over the past 5 years have yielded lessons on how to facilitate access to oral PrEP; expand service delivery for PrEP; address the knowledge, attitudes, and skills providers need to support PrEP initiation and effective use; develop messaging that builds community and partner support and combats stigma; and understand the cyclical nature of PrEP use. Evidence from oral PrEP introduction and scale-up can help inform and expedite DVR introduction.

Impact and experience of participant engagement activities in supporting dapivirine ring use among participants enrolled in the phase III MTN-020/ASPIRE study.

BACKGROUND: Low adherence to investigational products can negatively impact study outcomes, limiting the ability to demonstrate efficacy. To continue advancing potential new HIV prevention technologies, efforts are needed to improve adherence among study participants. In MTN-020/ASPIRE, a phase III randomized, double-blind, placebo-controlled study of the dapivirine vaginal ring carried out across 15 sites in sub-Saharan Africa, a multifaceted approach to adherence support was implemented, including a strong focus on participant engagement activities (PEAs). In this manuscript, we describe PEAs and participant attendance, and analyze the potential impact of PEAs on ring use. METHODS: All sites implemented PEAs and submitted activity and attendance reports to the study management team throughout the study. Participant demographics were collected via case report forms. Residual dapivirine remaining in the last ring returned by each participant was used to estimate drug released from the ring, which was then adjusted for time participants had the ring to calculate probable use categorized into three levels (low/intermittent/high). Product use was connected to PEA attendance using participant identification numbers. We used multivariate Poisson regression with robust standard errors to explore differences in ring use between PEA attendance groups and reviewed qualitative reports for illustrative quotes highlighting participant experiences with PEAs. RESULTS: 2312 of 2629 study participants attended at least one of 389 PEAs conducted across sites. Participant country and partner knowledge of study participation were most strongly associated with PEA attendance (p < 0.005) with age, education, and income status also associated with event attendance (p < 0.05). When controlling for these variables, participants who attended at least one event were more likely to return a last ring showing at least some use (RR = 1.40) than those who never attended an event. There was a stronger correlation between a last returned ring showing use and participant attendance at multiple events (RR = 1.52). CONCLUSIONS: Our analysis supports the growing body of work illustrating the importance of meaningfully engaging research participants to achieve study success and aligns with other analyses of adherence support efforts during ASPIRE. While causation between PEA attendance and product use cannot be established, residual drug levels in returned rings strongly correlated with participant attendance at PEAs, and the benefits of incorporating PEAs should be considered when designing future studies of investigational products.

Acceptability of the Dapivirine Vaginal Ring for HIV-1 Prevention and Association with Adherence in a Phase III Trial.

We evaluated the acceptability of the 25 mg dapivirine vaginal ring (DVR) as an HIV prevention intervention and its influence on DVR adherence in the MTN-020/ASPIRE phase III trial. Acceptability measures were captured using ACASI at month 3 and end of product use (median 24 months, IQR 15-30). Monthly returned rings were classified as nonadherent if dapivirine release rate was ≤ 0.9 mg/month. Associations between acceptability measures and nonadherence were estimated using Poisson regression models with robust standard errors. At month 3 (N = 2334), 88% reported DVR was comfortable, 80% were unaware of it during daily activities, and 74% never felt it during sex. At exit, 66% were 'very likely' to use DVR in the future. Acceptability was found to differ significantly by country across several measures including wearing the ring during sex, during menses, partner acceptability, impact on sexual pleasure and willingness to use the ring in the future. Risk of nonadherence at month 12 was elevated if DVR was felt during sex at month 3 (aRR 1.67, 95% CI 1.26, 2.23). Risk of nonadherence in the last year of study participation was elevated if, at exit, participants minded wearing during sex (aRR 2.08, 95% CI 1.52, 2.85), during menses (aRR 1.57, 95% CI 1.06, 2.32), reported a problematic change to the vaginal environment (aRR 1.57, 95% CI 1.12, 2.21), and were not "very likely" to use DVR in the future (aRR 1.31, 95% CI 1.02, 1.68). DVR acceptability was overall high yet varied by country. Addressing perceived ring interference with sex, menses, or problematic changes to the vaginal environment in future interventions could help improve adherence, as could embracing sex-positive messaging related to ring use and increased pleasure.Trial Registration ClinicalTrials.gov Identifier: NCT01617096.

Safety, uptake, and use of a dapivirine vaginal ring for HIV-1 prevention in African women (HOPE): an open-label, extension study.

BACKGROUND: Two phase 3 clinical trials showed that use of a monthly vaginal ring containing 25 mg dapivirine was well tolerated and reduced HIV-1 incidence in women by approximately 30% compared with placebo. We aimed to evaluate use and safety of the dapivirine vaginal ring (DVR) in open-label settings with high background rates of HIV-1 infection, an important step for future implementation. METHODS: We did a phase 3B open-label extension trial of the DVR (MTN-025/HIV Open-label Prevention Extension [HOPE]). Women who were HIV-1-negative and had participated in the MTN-020/ASPIRE phase 3 trial were offered 12 months of access to the DVR at 14 clinical research centres in Malawi, South Africa, Uganda, and Zimbabwe. At each visit (monthly for 3 months, then once every 3 months), women chose whether or not to accept the offer of the ring. Used, returned rings were tested for residual amounts of dapivirine as a surrogate marker for adherence. HIV-1 serological testing was done at each visit. Dapivirine amounts in returned rings and HIV-1 incidence were compared with data from the ASPIRE trial, and safety was assessed. This study is registered with ClinicalTrials.gov, NCT02858037. FINDINGS: Between July 16, 2016, and Oct 10, 2018, of 1756 women assessed for eligibility, 1456 were enrolled and participated in the study. Median age was 31 years (IQR 27-37). At baseline, 1342 (92·2%) women chose to take the DVR; ring acceptance was more than 79% at each visit up until 12 months and 936 (73·2%) of 1279 chose to take the ring at all visits. 12 530 (89·3%) of 14 034 returned rings had residual dapivirine amounts consistent with some use during the previous month (>0·9 mg released) and the mean dapivirine amount released was greater than in the ASPIRE trial (by 0·21 mg; p<0·0001). HIV-1 incidence was 2·7 per 100 person-years (95% CI 1·9-3·8, 35 infections), compared with an expected incidence of 4·4 per 100 person-years (3·2-5·8) among a population matched on age, site, and presence of a sexually transmitted infection from the placebo group of ASPIRE. No serious adverse events or grade 3 or higher adverse events observed were assessed as related to the DVR. INTERPRETATION: High uptake and persistent use in this open-label extension study support the DVR as an HIV-1 prevention option for women. With an increasing number of HIV-1 prophylaxis choices on the horizon, these results suggest that the DVR will be an acceptable and practical option for women in Africa. FUNDING: The Microbicide Trials Network and the National Institute of Allergy and Infectious Diseases, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health, all components of the US National Institutes of Health.

Integrating Oral PrEP Into Family Planning Services for Women in Sub-saharan Africa: Findings From a Multi-Country Landscape Analysis.

Integration of HIV and family planning (FP) services is a renewed focus area for national policymakers, donors, and implementers in sub-Saharan Africa as a result of high HIV incidence among general-population women, especially adolescent girls and young women (AGYW), and the perception that integrating HIV pre-exposure prophylaxis (PrEP) into FP services may be an effective way to provide comprehensive HIV and FP services to this population. We conducted a focused desk review to develop a PrEP-FP integration framework across five key categories: plans and policies, resource management, service delivery, PrEP use, and monitoring and reporting. The framework was refined via interviews with 30 stakeholders across seven countries at varying stages of oral PrEP rollout: Kenya, Lesotho, Malawi, South Africa, Uganda, Zambia, and Zimbabwe. After refining the framework, we developed a PrEP-FP integration matrix and assessed country-specific progress to identify common enablers of and barriers to PrEP-FP integration. None of the countries included in our analysis had made substantial progress toward integrated PrEP-FP service delivery. Although the countries made progress in one or two categories, integration was often impeded by lack of advancement in other areas. Our framework offers policymakers, program implementers, and health care providers a road map for strategically assessing and monitoring progress toward PrEP-FP integration in their contexts.

Oral preexposure prophylaxis continuation, measurement and reporting.

OBJECTIVE: The aim of this study was to appropriately plan for rollout and monitor impact of oral preexposure prophylaxis (PrEP). It is important to understand PrEP continuation and come to a consensus on how best to measure PrEP continuation. This study reviews data on PrEP continuation to document how it is reported, and to compare continuation over time and across populations. DESIGN: A systematic review and meta-analysis. METHODS: We searched MEDLINE, Embase and Global Health and reviewed abstracts from HIV conferences from 2017 to 2018 for studies reporting primary data on PrEP continuation. Findings were summarized along a PrEP cascade and continuation was presented by population at months 1, 6 and 12, with random-effects meta-analysis. RESULTS: Of 2578 articles and 596 abstracts identified, 41 studies were eligible covering 22 034 individuals. Continuation data were measured and reported inconsistently. Results showed high discontinuation at month 1 and persistent discontinuation at later time points in many studies. Pooled continuation estimates were 66% at month 1 [n = 5348; 95% confidence interval (95% CI): 48-82], 63% at month 6 (n = 13 629; 95% CI: 48-77) and 71% at month 12 (n = 14 933; 95% CI: 60-81; higher estimate than previous timepoints due to inclusion of different studies). Adequate data were not available to reliably compare estimates across populations. CONCLUSION: This review found that discontinuation at one month was high, suggesting PrEP initiations may be a poor measure of effectiveness. Continuation declined further over time in many studies, indicating existing cross-sectional indicators may not be adequate to understand PrEP use patterns. Studies do not measure continuation consistently, and consensus is needed.

Vaginal ring acceptability and related preferences among women in low- and middle-income countries: A systematic review and narrative synthesis.

The vaginal ring (VR) is a female-initiated drug-delivery platform used for different indications, including HIV pre-exposure prophylaxis (PrEP). We conducted a systematic review of VR acceptability, values and preferences among women in low- and middle-income countries (LMIC) to inform further investment and/or guidance on VR use for HIV prevention. Following PRISMA guidelines, we used structured methods to search, screen, and extract data from randomized controlled trials (RCTs) and observational studies reporting quantitative outcomes of acceptability of the VR for any indication published 1/1970-2/2019 (PROSPERO: CRD42019122220). Of 1,110 records identified, 68 met inclusion criteria. Studies included women 15-50+ years from 25 LMIC for indications including HIV prevention, contraception, abnormal bleeding, and menopause. Overall VR acceptability was high (71-98% across RCTs; 62-100% across observational studies), with 80-100% continuation rates in RCTs and favorable ease of insertion (greater than 85%) and removal 89-99%). Users reported concerns about the VR getting lost in the body (8-43%), although actual expulsions and adverse events were generally infrequent. Most women disclosed use to partners, with some worrying about partner anger/violence. The VR was not felt during intercourse by 70-92% of users and 48-97% of partners. Acceptability improved over time both within studies (as women gained VR experience and worries diminished), and over chronological time (as the device was popularized). Women expressed preferences for accessible, long-acting, partner-approved methods that prevent both HIV and pregnancy, can be used without partner knowledge, and have no impact on sex and few side effects. This review was limited by a lack of standardization of acceptability measures and study heterogeneity. This systematic review suggests that most LMIC women users have a positive view of the VR that increases with familiarity of use; and, that many would consider the VR an acceptable future delivery device for HIV prevention or other indications.

Social harms in female-initiated HIV prevention method research: state of the evidence.

OBJECTIVES: Assessment of safety is an integral part of real-time monitoring in clinical trials. In HIV prevention research, safety of investigational products and trial participation has been expanded to include monitoring for 'social harms', generally defined as negative consequences of trial participation that may manifest in social, psychological, or physical ways. Further research on social harms within HIV prevention research is needed to understand the potential safety risks for women and advance the implementation of prevention methods in real-world contexts. METHODS: Secondary analysis of quantitative data from three randomized, double-blind, placebo-controlled trials of microbicide candidates in sub-Saharan Africa was conducted. Additionally, we assessed data from two prospective cohort studies that included participants who became HIV-positive or pregnant during parent trials. RESULTS: Social harms reporting was low across the largest and most recent microbicide studies. Social harm incidence per 100 person-years ranged from 1.10 (95% CI 0.78-1.52) to 3.25 (95% CI 2.83-3.74) in the phased trials. Reporting differed by dosing mechanism (e.g. vaginal gel, oral tablet, ring) and study, most likely as a function of measurement differences. Social harms were most frequently associated with male partners, rather than, for example, experiences of stigma in the community. CONCLUSION: Measurement and screening for social harms is an important component of conducting ethical research of novel HIV prevention methods. To date, social harm incidence reported in microbicide trials has been relatively low (<4% per 100 person-years), and the majority have been partner-related events. However, any incidence of social harm within the context of HIV prevention is important to capture and understand for the safety of individuals, and for the successful impact of prevention methods in a real-world context.

Evaluating the potential impact and cost-effectiveness of dapivirine vaginal ring pre-exposure prophylaxis for HIV prevention.

BACKGROUND: Expanded HIV prevention options are needed to increase uptake of HIV prevention among women, especially in generalized epidemics. As the dapivirine vaginal ring moves forward through regulatory review and open-label extension studies, the potential public health impact and cost-effectiveness of this new prevention method are not fully known. We used mathematical modeling to explore the impact and cost-effectiveness of the ring in different implementation scenarios alongside scale-up of other HIV prevention interventions. Given the knowledge gaps about key factors influencing the ring's implementation, including potential uptake and delivery costs, we engaged in a stakeholder consultation process to elicit plausible parameter ranges and explored scenarios to identify the possible range of impact, cost, and cost-effectiveness. METHODS AND FINDINGS: We used the Goals model to simulate scenarios of oral and ring pre-exposure prophylaxis (PrEP) implementation among female sex workers and among other women ≤21 years or >21 years with multiple male partners, in Kenya, South Africa, Uganda, and Zimbabwe. In these scenarios, we varied antiretroviral therapy (ART) coverage, dapivirine ring coverage and ring effectiveness (encompassing efficacy and adherence) by risk group. Following discussions with stakeholders, the maximum level of PrEP coverage (oral and/or ring) considered in each country was equal to modern contraception use minus condom use in the two age groups. We assessed results for 18 years, from 2018 to 2035. In South Africa, for example, the HIV infections averted by PrEP (ring plus oral PrEP) ranged from 310,000 under the highest-impact scenario (including ART held constant at 2017 levels, high ring coverage, and 85% ring effectiveness) to 55,000 under the lowest-impact scenario (including ART reaching the UNAIDS 90-90-90 targets by 2020, low ring coverage, and 30% ring effectiveness). This represented a range of 6.4% to 2.2% of new HIV infections averted. Given our assumptions, the addition of the ring results in 11% to 132% more impact than oral PrEP alone. The cost per HIV infection averted for the ring ranged from US$13,000 to US$121,000. CONCLUSIONS: This analysis offers a wide range of scenarios given the considerable uncertainty over ring uptake, consistency of use, and effectiveness, as well as HIV testing, prevention, and treatment use over the next two decades. This could help inform donors and implementers as they decide where to allocate resources in order to maximize the impact of the dapivirine ring in light of funding and implementation constraints. Better understanding of the cost and potential uptake of the intervention would improve our ability to estimate its cost-effectiveness and assess where it can have the most impact.

PrEP Communications Accelerator: a digital demand creation tool for sub-Saharan Africa.

Background Strategic communications are critical for successful market introduction of oral pre-exposure prophylaxis (PrEP). This paper focuses on the OPTIONS Consortium's approach to developing the PrEP Communications Accelerator, a digital tool that provides communication strategies and tools for generating demand for PrEP across sub-Saharan Africa. METHODS: The PrEP Communications Accelerator was developed through needs assessment, communications landscape and gap analysis, market research and content development and testing. Stakeholder consultations across multiple African countries and audiences were conducted to validate and refine findings at each step. RESULTS: The PrEP Communications Accelerator provides customised communications plans that vary by target audience (adolescent girls and young women, female sex workers, serodiscordant couples, men who have sex with men, people who inject drugs and the general population) and by setting (clinic, community, subnational or national level). Users of the interactive tool receive custom-built demand creation strategy guidance, including suggested media channels and communication tactics based on available evidence about the population and setting. DISCUSSION: The PrEP Communications Accelerator is a digital demand creation tool intended to equip those who work in resource- and time-constrained environments with the evidence-based guidance needed to jump-start local demand creation efforts. The tool provides guidance on strategic PrEP communications for target audiences most at risk of HIV infection, as well as a broad profile of the general population to cultivate support for PrEP as a new public health product.

Understanding and measuring uptake and coverage of oral pre-exposure prophylaxis delivery among adolescent girls and young women in sub-Saharan Africa.

In response to World Health Organization (WHO) guidance recommending oral pre-exposure prophylaxis (PrEP) for all individuals at substantial risk for HIV infection, significant investments are being made to expand access to oral PrEP globally, particularly in sub-Saharan Africa. Some have interpreted early monitoring reports from new programs delivering oral PrEP to adolescent girls and young women (AGYW) as suggestive of low uptake. However, a lack of common definitions complicates interpretation of oral PrEP uptake and coverage measures, because various indicators with different meanings and uses are used interchangeably. Furthermore, operationalising these measures in real-world settings is challenged by the difficulties in defining the denominator for measuring uptake and coverage among AGYW, due to the lack of data and experience required to identify the subset of AGYW at substantial risk of HIV infection. This paper proposes an intervention-centric cascade as a framework for developing a common lexicon of metrics for uptake and coverage of oral PrEP among AGYW. In codifying these indicators, approaches to clearly define metrics for uptake and coverage are outlined, and the discussion on 'low' uptake is reframed to focus on achieving the highest possible proportion of AGYW using oral PrEP when they need and want it Recommendations are also provided for making increased investments in implementation research to better quantify the sub-group of AGYW in potential need of oral PrEP.and for improving monitoring systems to more efficiently address bottlenecks in the service delivery of oral PrEP to AGYW so that implementation can be taken to scale.