Understanding the Evolving Role of Voluntary Medical Male Circumcision as a Public Health Strategy in Eastern and Southern Africa: Opportunities and Challenges.

PURPOSE OF REVIEW: Voluntary male medical circumcision (VMMC) has been a cornerstone of HIV prevention in Eastern and Southern Africa (ESA) and is credited in part for declines in HIV incidence seen in recent years. However, these HIV incidence declines change VMMC cost-effectiveness and how it varies across populations. RECENT FINDINGS: Mathematical models project continued cost-effectiveness of VMMC in much of ESA despite HIV incidence declines. A key data gap is how demand generation cost differs across age groups and over time as VMMC coverage increases. Additionally, VMMC models usually neglect non-HIV effects of VMMC, such as prevention of other sexually transmitted infections and medical adverse events. While small compared to HIV effects in the short term, these could become important as HIV incidence declines. Evidence to date supports prioritizing VMMC in ESA despite falling HIV incidence. Updated modeling methodologies will become necessary if HIV incidence reaches low levels.

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.

Time to Scale Up Preexposure Prophylaxis Beyond the Highest-Risk Populations? Modeling Insights From High-Risk Women in Sub-Saharan Africa.

OBJECTIVES: New HIV infections remain higher in women than men in sub-Saharan Africa. Preexposure prophylaxis (PrEP) is an effective HIV prevention measure, currently prioritized for those at highest risk, such as female sex workers (FSWs), for whom it is most cost-effective. However, the greatest number of HIV infections in sub-Saharan Africa occurs in women in the general population. As countries consider wider PrEP scale-up, there is a need to weigh the population-level impact, cost, and relative cost-effectiveness to inform priority setting. METHODS: We developed mathematical models of HIV risk to women and derived tools to highlight key considerations for PrEP programming. The models were fitted to South Africa, Zimbabwe, and Kenya, spanning a range of HIV burden in sub-Saharan Africa. The impact, cost, and cost-effectiveness of PrEP scale-up for adolescent girls and young women (AGYW), women 25 to 34 years old, and women 35 to 49 years old were assessed, accounting for differences in population sizes and the low program retention levels reported in demonstration projects. RESULTS: Preexposure prophylaxis could avert substantially more infections a year among women in general population than among FSW. The greatest number of infections could be averted annually among AGYW in South Africa (24-fold that for FSW). In Zimbabwe, the greatest number of infections could be averted among women 25 to 34 years old (8-fold that for FSW); and in Kenya, similarly between AGYW and women 25 to 34 years old (3-fold that for FSW). However, the unit costs of PrEP delivery for AGYW, women 25 to 34 years old, and women 35 to 49 years old would have to reduce considerably (by 70.8%-91.0% across scenarios) for scale-up to these populations to be as cost-effective as for FSW. CONCLUSIONS: Preexposure prophylaxis has the potential to substantially reduce new HIV infections in HIV-endemic countries in sub-Saharan Africa. This will necessitate PrEP being made widely available beyond those at highest individual risk and continued integration into a range of national services and at community level to significantly bring down the costs and improve cost-effectiveness.

Voluntary Medical Male Circumcision to Prevent HIV: Modelling Age Prioritization in Namibia.

Voluntary Medical Male circumcision (VMMC) has been part of prevention in Namibia since 2009. Yet, as of 2013, VMMC coverage among 15- to 24-year-olds was estimated at less than 22%. Program data suggests uptake of VMMC below age 15 is lower than expected, given the age distribution of the eligible population. Nearly 85% of VMMCs were for males between ages 15 and 29, while boys 10-14 years were referred outside the program. This analysis uses the Decision Makers Program Planning Tool to understand the impact of age prioritization on circumcision in Namibia. Results indicate that circumcising males aged 20-29 reduced HIV incidence most rapidly, while focusing on ages 15-24 was more cost effective and produced greater magnitude of impact. Providing services to those under 15 could increase VMMC volume 67% while introducing Early Infant Medical Circumcision could expand coverage. This exercise supported a review of VMMC strategies and implementation, with Namibia increasing coverage among 10- to 14-year-olds nearly 20 times from 2016 to 2017.

Scaling Up Voluntary Medical Male Circumcision for Human Immunodeficiency Virus Prevention for Adolescents and Young Adult Men: A Modeling Analysis of Implementation and Impact in Selected Countries.

Background: The new World Health Organization and Joint United Nations Programme on HIV/AIDS strategic framework for voluntary medical male circumcision (VMMC) aims to increase VMMC coverage among males aged 10-29 years in priority settings to 90% by 2021. We use mathematical modeling to assess the likelihood that selected countries will achieve this objective, given their historical VMMC progress and current implementation options. Methods: We use the Decision Makers' Program Planning Toolkit, version 2, to examine 4 ambitious but feasible scenarios for scaling up VMMC coverage from 2017 through 2021, inclusive in Lesotho, Malawi, Mozambique, Namibia, South Africa, Swaziland, Tanzania, Uganda, and Zimbabwe. Results: Tanzania is the only country that would reach the goal of 90% VMMC coverage in 10- to 29-year-olds by the end of 2021 in the scenarios assessed, and this was true in 3 of the scenarios studied. Mozambique, South Africa, and Lesotho would come close to reaching the objective only in the most ambitious scenario examined. Conclusions: Major changes in VMMC implementation in most countries will be required to increase the proportion of circumcised 10- to 29-year-olds to 90% by the end of 2021. Scaling up VMMC coverage in males aged 10-29 years will require significantly increasing the number of circumcisions provided to 10- to 14-year-olds and 15- to 29-year-olds.

Bridging the divide: HIV prevention research and Black men who have sex with men.

OBJECTIVES: We obtained contextual information regarding documented barriers to HIV clinical trial participation among Black men who have sex with men (MSM), and explored current preventive HIV clinical trial attitudes, beliefs, and perceptions among Black MSM leaders in the United States. METHODS: We conducted 2 focus groups with Black MSM leaders attending an annual African American MSM Leadership Conference on HIV/AIDS. Focus group questions explored biomedical research perceptions and attitudes, barriers to participation in biomedical prevention research, and steps that need to be taken to address these barriers. A feedback and member checking (participants presented with final themes to provide feedback and guidance) session was also held at the 2012 conference. RESULTS: Three distinct themes emerged regarding Black MSM engagement and participation in HIV vaccine research: (1) community-based organizations as true partners, (2) investment in the Black gay community, and (3) true efforts to inform and educate the community. CONCLUSIONS: A key focus for improving efforts to engage the Black MSM community in preventive HIV clinical trials is building and maintaining equitable and reciprocal partnerships among research institutions, Black-led AIDS service organizations and community-based organizations, and community members.

Substantial but spatially heterogeneous progress in male circumcision for HIV prevention in South Africa.

BACKGROUND: Voluntary medical male circumcision (VMMC) reduces the risk of male HIV acquisition by 60%. Programmes to provide VMMCs for HIV prevention have been introduced in sub-Saharan African countries with high HIV burden. Traditional circumcision is also a long-standing male coming-of-age ritual, but practices vary considerably across populations. Accurate estimates of circumcision coverage by age, type, and time at subnational levels are required for planning and delivering VMMCs to meet targets and evaluating their impacts on HIV incidence. METHODS: We developed a Bayesian competing risks time-to-event model to produce region-age-time-type specific probabilities and coverage of male circumcision with probabilistic uncertainty. The model jointly synthesises data from household surveys and health system data on the number of VMMCs conducted. We demonstrated the model using data from five household surveys and VMMC programme data to produce estimates of circumcision coverage for 52 districts in South Africa between 2008 and 2019. RESULTS: Nationally, in 2008, 24.1% (95% CI: 23.4-24.8%) of men aged 15-49 were traditionally circumcised and 19.4% (18.9-20.0%) were medically circumcised. Between 2010 and 2019, 4.25 million VMMCs were conducted. Circumcision coverage among men aged 15-49 increased to 64.0% (63.2-64.9%) and medical circumcision coverage to 42% (41.3-43.0%). Circumcision coverage varied widely across districts, ranging from 13.4 to 86.3%. The average age of traditional circumcision ranged between 13 and 19 years, depending on local cultural practices. CONCLUSION: South Africa has made substantial, but heterogeneous, progress towards increasing medical circumcision coverage. Detailed subnational information on coverage and practices can guide programmes to identify unmet need to achieve national and international targets.

Voluntary medical male circumcision reduces the risk of male HIV acquisition. Programmes to provide circumcisions for HIV prevention have been introduced in sub-Saharan African countries with high HIV burden. Estimates of circumcision coverage are needed for planning and delivering circumcisions to meet targets and evaluate their impacts on HIV incidence. We developed a model to integrate date from both household surveys and health systems on the number of circumcisions conducted, and applied it to understand how the practices and coverage of circumcision are changing in South Africa. National circumcision coverage increased considerably between 2008 and 2019, however, there remains a substantial subnational variation across districts and age groups. Further progress is needed to reach national and international targets.

Lessons learnt from daily oral PrEP delivery to inform national planning for PrEP ring introduction for women in low-income and middle-income countries: a qualitative inquiry of international stakeholders.

INTRODUCTION: Some African countries plan to introduce and scale-up new long-acting pre-exposure prophylaxis methods (LA-PrEP), like the monthly dapivirine vaginal ring (PrEP ring) and injectable cabotegravir. National costed implementation plans, roadmaps for successful product implementation, are often overlooked. International stakeholders engaged in oral PrEP planning, introduction and scale-up are an information resource of lessons learned to advise LA-PrEP planning. We consulted such international stakeholders and synthesised oral PrEP lessons to inform the development of a costed rollout plan template for LA-PrEP. METHODS: From selected global health organisations (five international nongovernmental, four donor, four university/research and two multilateral), we interviewed 27 representatives based in America, Europe, Asia and Africa about strategic content and approaches for LA-PrEP policy, programming and implementation. We conducted a thematic analysis of the interview data for implementation considerations. RESULTS: From the consultations, we identified six implementation themes for LA-PrEP introduction and scale-up: (1) ethically increasing choice and avoiding coercion; (2) de-stigmatising PrEP by focusing on preference rather than risk-based eligibility; (3) integrating LA-PrEP into services that are more woman-oriented, couple-oriented and family-oriented, and providing private spaces for LA-PrEP delivery; (4) de-medicalising delivery of relatively safe products (eg, PrEP ring); (5) constructing multilevel, nuanced communication strategies to address measured and perceived product efficacy and effectiveness; and (6) devising product-agnostic, modular approaches to service delivery. Despite the widespread emphasis on integration, few stakeholders offered empirical examples of successful integration approaches and frameworks. CONCLUSIONS: Lessons learnt from stakeholder participants suggest standardised and modular processes can improve efficiencies in LA-PrEP planning and implementation. Tiered communication strategies addressing product efficacy and effectiveness will improve clients' and providers' efficacy in making informed decisions. Integration is important for LA-PrEP delivery, but data on empirical integration approaches and frameworks is minimal: further research in this discipline is needed.

Implementation and resource needs for long-acting PrEP in low- and middle-income countries: a scoping review.

INTRODUCTION: Several low- and middle-income countries (LMICs) are preparing to introduce long-acting pre-exposure prophylaxis (LAP). Amid multiple pre-exposure prophylaxis (PrEP) options and constrained funding, decision-makers could benefit from systematic implementation planning and aligned costs. We reviewed national costed implementation plans (CIPs) to describe relevant implementation inputs and activities (domains) for informing the costed rollout of LAP. We assessed how primary costing evidence aligned with those domains. METHODS: We conducted a rapid review of CIPs for oral PrEP and family planning (FP) to develop a consensus of implementation domains, and a scoping review across nine electronic databases for publications on PrEP costing in LMICs between January 2010 and June 2022. We extracted cost data and assessed alignment with the implementation domains and the Global Health Costing Consortium principles. RESULTS: We identified 15 implementation domains from four national PrEP plans and FP-CIP template; only six were in all sources. We included 66 full-text manuscripts, 10 reported LAP, 13 (20%) were primary cost studies-representing seven countries, and none of the 13 included LAP. The 13 primary cost studies included PrEP commodities (n = 12), human resources (n = 11), indirect costs (n = 11), other commodities (n = 10), demand creation (n = 9) and counselling (n = 9). Few studies costed integration into non-HIV services (n = 5), above site costs (n = 3), supply chains and logistics (n = 3) or policy and planning (n = 2), and none included the costs of target setting, health information system adaptations or implementation research. Cost units and outcomes were variable (e.g. average per person-year). DISCUSSION: LAP planning will require updating HIV prevention policies, technical assistance for logistical and clinical support, expanding beyond HIV platforms, setting PrEP achievement targets overall and disaggregated by method, extensive supply chain and logistics planning and support, as well as updating health information systems to monitor multiple PrEP methods with different visit schedules. The 15 implementation domains were variable in reviewed studies. PrEP primary cost and budget data are necessary for new product introduction and should match implementation plans with financing. CONCLUSIONS: As PrEP services expand to include LAP, decision-makers need a framework, tools and a process to support countries in planning the systematic rollout and costing for LAP.

Cost-effectiveness of voluntary medical male circumcision for HIV prevention across sub-Saharan Africa: results from five independent models.

BACKGROUND: Voluntary medical male circumcision (VMMC) has been a recommended HIV prevention strategy in sub-Saharan Africa since 2007, particularly in countries with high HIV prevalence. However, given the scale-up of antiretroviral therapy programmes, it is not clear whether VMMC still represents a cost-effective use of scarce HIV programme resources. METHODS: Using five existing well described HIV mathematical models, we compared continuation of VMMC for 5 years in men aged 15 years and older to no further VMMC in South Africa, Malawi, and Zimbabwe and across a range of setting scenarios in sub-Saharan Africa. Outputs were based on a 50-year time horizon, VMMC cost was assumed to be US$90, and a cost-effectiveness threshold of US$500 was used. FINDINGS: In South Africa and Malawi, the continuation of VMMC for 5 years resulted in cost savings and health benefits (infections and disability-adjusted life-years averted) according to all models. Of the two models modelling Zimbabwe, the continuation of VMMC for 5 years resulted in cost savings and health benefits by one model but was not as cost-effective according to the other model. Continuation of VMMC was cost-effective in 68% of setting scenarios across sub-Saharan Africa. VMMC was more likely to be cost-effective in modelled settings with higher HIV incidence; VMMC was cost-effective in 62% of settings with HIV incidence of less than 0·1 per 100 person-years in men aged 15-49 years, increasing to 95% with HIV incidence greater than 1·0 per 100 person-years. INTERPRETATION: VMMC remains a cost-effective, often cost-saving, prevention intervention in sub-Saharan Africa for at least the next 5 years. FUNDING: Bill & Melinda Gates Foundation for the HIV Modelling Consortium.

Predicted effects of the introduction of long-acting injectable cabotegravir pre-exposure prophylaxis in sub-Saharan Africa: a modelling study.

BACKGROUND: Long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) is recommended by WHO as an additional option for HIV prevention in sub-Saharan Africa, but there is concern that its introduction could lead to an increase in integrase-inhibitor resistance undermining treatment programmes that rely on dolutegravir. We aimed to project the health benefits and risks of cabotegravir-PrEP introduction in settings in sub-Saharan Africa. METHODS: With HIV Synthesis, an individual-based HIV model, we simulated 1000 setting-scenarios reflecting both variability and uncertainty about HIV epidemics in sub-Saharan Africa and compared outcomes for each with and without cabotegravir-PrEP introduction. PrEP use is assumed to be risk-informed and to be used only in 3-month periods (the time step for the model) when having condomless sex. We consider three groups at risk of integrase-inhibitor resistance emergence: people who start cabotegravir-PrEP after (unknowingly) being infected with HIV, those who seroconvert while on PrEP, and those with HIV who have residual cabotegravir drugs concentrations during the early tail period after recently stopping PrEP. We projected the outcomes of policies of cabotegravir-PrEP introduction and of no introduction in 2022 across 50 years. In 50% of setting-scenarios we considered that more sensitive nucleic-acid-based HIV diagnostic testing (NAT), rather than regular antibody-based HIV rapid testing, might be used to reduce resistance risk. For cost-effectiveness analysis we assumed in our base case a cost of cabotegravir-PrEP drug to be similar to oral PrEP, resulting in a total annual cost of USD$144 per year ($114 per year and $264 per year considered in sensitivity analyses), a cost-effectiveness threshold of $500 per disability-adjusted life years averted, and a discount rate of 3% per year. FINDINGS: Reflecting our assumptions on the appeal of cabotegravir-PrEP, its introduction is predicted to lead to a substantial increase in PrEP use with approximately 2·6% of the adult population (and 46% of those with a current indication for PrEP) receiving PrEP compared with 1·5% (28%) without cabotegravir-PrEP introduction across 20 years. As a result, HIV incidence is expected to be lower by 29% (90% range across setting-scenarios 6-52%) across the same period compared with no introduction of cabotegravir-PrEP. In people initiating antiretroviral therapy, the proportion with integrase-inhibitor resistance after 20 years is projected to be 1·7% (0-6·4%) without cabotegravir-PrEP introduction but 13·1% (4·1-30·9%) with. Cabotegravir-PrEP introduction is predicted to lower the proportion of all people on antiretroviral therapy with viral loads less than 1000 copies per mL by 0·9% (-2·5% to 0·3%) at 20 years. For an adult population of 10 million an overall decrease in number of AIDS deaths of about 4540 per year (-13 000 to -300) across 50 years is predicted, with little discernible benefit with NAT when compared with standard antibody-based rapid testing. AIDS deaths are predicted to be averted with cabotegravir-PrEP introduction in 99% of setting-scenarios. Across the 50-year time horizon, overall HIV programme costs are predicted to be similar regardless of whether cabotegravir-PrEP is introduced (total mean discounted annual HIV programme costs per year across 50 years is $151·3 million vs $150·7 million), assuming the use of standard antibody testing. With antibody-based rapid HIV testing, the introduction of cabotegravir-PrEP is predicted to be cost-effective under an assumed threshold of $500 per disability-adjusted life year averted in 82% of setting-scenarios at the cost of $144 per year, in 52% at $264, and in 87% at $114. INTERPRETATION: Despite leading to increases in integrase-inhibitor drug resistance, cabotegravir-PrEP introduction is likely to reduce AIDS deaths in addition to HIV incidence. Long-acting cabotegravir-PrEP is predicted to be cost-effective if delivered at similar cost to oral PrEP with antibody-based rapid HIV testing. FUNDING: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

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.

Cost-effectiveness of easy-access, risk-informed oral pre-exposure prophylaxis in HIV epidemics in sub-Saharan Africa: a modelling study.

BACKGROUND: Approaches that allow easy access to pre-exposure prophylaxis (PrEP), such as over-the-counter provision at pharmacies, could facilitate risk-informed PrEP use and lead to lower HIV incidence, but their cost-effectiveness is unknown. We aimed to evaluate conditions under which risk-informed PrEP use is cost-effective. METHODS: We applied a mathematical model of HIV transmission to simulate 3000 setting-scenarios reflecting a range of epidemiological characteristics of communities in sub-Saharan Africa. The prevalence of HIV viral load greater than 1000 copies per mL among all adults (HIV positive and negative) varied from 1·1% to 7·4% (90% range). We hypothesised that if PrEP was made easily available without restriction and with education regarding its use, women and men would use PrEP, with sufficient daily adherence, during so-called seasons of risk (ie, periods in which individuals are at risk of acquiring infection). We refer to this as risk-informed PrEP. For each setting-scenario, we considered the situation in mid-2021 and performed a pairwise comparison of the outcomes of two policies: immediate PrEP scale-up and then continuation for 50 years, and no PrEP. We estimated the relationship between epidemic and programme characteristics and cost-effectiveness of PrEP availability to all during seasons of risk. For our base-case analysis, we assumed a 3-monthly PrEP cost of US$29 (drug $11, HIV test $4, and $14 for additional costs necessary to facilitate education and access), a cost-effectiveness threshold of $500 per disability-adjusted life-year (DALY) averted, an annual discount rate of 3%, and a time horizon of 50 years. In sensitivity analyses, we considered a cost-effectiveness threshold of $100 per DALY averted, a discount rate of 7% per annum, the use of PrEP outside of seasons of risk, and reduced uptake of risk-informed PrEP. FINDINGS: In the context of PrEP scale-up such that 66% (90% range across setting-scenarios 46-81) of HIV-negative people with at least one non-primary condomless sex partner take PrEP in any given period, resulting in 2·6% (0·9-6·0) of all HIV negative adults taking PrEP at any given time, risk-informed PrEP was predicted to reduce HIV incidence by 49% (23-78) over 50 years compared with no PrEP. PrEP was cost-effective in 71% of all setting-scenarios, and cost-effective in 76% of setting-scenarios with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%. In sensitivity analyses with a $100 per DALY averted cost-effectiveness threshold, a 7% per year discount rate, or with PrEP use that was less well risk-informed than in our base case, PrEP was less likely to be cost-effective, but generally remained cost-effective if the prevalence of HIV viral load greater than 1000 copies per mL among all adults was higher than 3%. In sensitivity analyses based on additional setting-scenarios in which risk-informed PrEP was less extensively used, the HIV incidence reduction was smaller, but the cost-effectiveness of risk-informed PrEP was undiminished. INTERPRETATION: Under the assumption that making PrEP easily accessible for all adults in sub-Saharan Africa in the context of community education leads to risk-informed use, PrEP is likely to be cost-effective in settings with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%, suggesting the need for implementation of such approaches, with ongoing evaluation. FUNDING: US Agency for International Development, US President's Emergency Plan for AIDS Relief, and Bill & Melinda Gates Foundation.

Estimating male circumcision coverage in 15 priority countries in sub-Saharan Africa.

INTRODUCTION: Given the importance of voluntary medical male circumcision (VMMC) in reducing HIV incidence, access to and use of quality data for programme planning and management are essential. Unfortunately, such data are currently not standardized for reliable and consistent programme use in priority countries. To redress this, the UNAIDS Reference Group (RG) on Estimates, Modelling, and Projection worked with partner Avenir Health to use the Decision Makers Program Planning Toolkit (DMPPT) 2 Online to provide estimates of VMMC coverage and to support countries to set age- and geographic-specific targets. This article describes the methods and tools used for assembling, reviewing and validating VMMC programme data as part of the 2021 Estimates process. DISCUSSION: The approach outlined for integrating VMMC data using the DMPPT2 Online required significant country engagement as well as upgrades to the DMPPT2 Online. The process brought together local-level VMMC stakeholders, for example Ministries of Health, the Joint United Nations Programme on HIV/AIDS (UNAIDS), the US President's Emergency Plan for AIDS Relief, the World Health Organization (WHO), VMMC implementers and so on, to review, amend and agree on historical and more recent VMMC data. The DMPPT2 Online was upgraded to align with the Spectrum and Naomi models used in the Annual HIV Estimates process. In addition, new and revised inputs were incorporated to enhance accuracy of modelled outputs. The process was successful in mobilizing stakeholders behind efforts to integrate VMMC into the annual HIV Estimates process and generating comprehensive, country-owned and validated VMMC data that will enhance programme monitoring and planning. CONCLUSIONS: VMMC programme data from most of the priority countries were successfully reviewed, updated, validated and incorporated into the annual HIV Estimates process in 2020. It is important to ensure that these data continue to be used for programme planning and management. Current and future data issues will need to be addressed, and countries will need ongoing support to do so. The integration of the DMPPT2 Online into the annual HIV Estimates process is a positive step forward in terms of streamlining country-owned planning and analytical practices for the HIV response.

Individual and community-level benefits of PrEP in western Kenya and South Africa: Implications for population prioritization of PrEP provision.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is highly effective in preventing HIV and has the potential to significantly impact the HIV epidemic. Given limited resources for HIV prevention, identifying PrEP provision strategies that maximize impact is critical. METHODS: We used a stochastic individual-based network model to evaluate the direct (infections prevented among PrEP users) and indirect (infections prevented among non-PrEP users as a result of PrEP) benefits of PrEP, the person-years of PrEP required to prevent one HIV infection, and the community-level impact of providing PrEP to populations defined by gender and age in western Kenya and South Africa. We examined sensitivity of results to scale-up of antiretroviral therapy (ART) and voluntary medical male circumcision (VMMC) by comparing two scenarios: maintaining current coverage ("status quo") and rapid scale-up to meet programmatic targets ("fast-track"). RESULTS: The community-level impact of PrEP was greatest among women aged 15-24 due to high incidence, while PrEP use among men aged 15-24 yielded the highest proportion of indirect infections prevented in the community. These indirect infections prevented continue to increase over time (western Kenya: 0.4-5.5 (status quo); 0.4-4.9 (fast-track); South Africa: 0.5-1.8 (status quo); 0.5-3.0 (fast-track)) relative to direct infections prevented among PrEP users. The number of person-years of PrEP needed to prevent one HIV infection was lower (59 western Kenya and 69 in South Africa in the status quo scenario; 201 western Kenya and 87 in South Africa in the fast-track scenario) when PrEP was provided only to women compared with only to men over time horizons of up to 5 years, as the indirect benefits of providing PrEP to men accrue in later years. CONCLUSIONS: Providing PrEP to women aged 15-24 prevents the greatest number of HIV infections per person-year of PrEP, but PrEP provision for young men also provides indirect benefits to women and to the community overall. This finding supports existing policies that prioritize PrEP use for young women, while also illuminating the community-level benefits of PrEP availability for men when resources permit.

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.

Modelling impact and cost-effectiveness of oral pre-exposure prophylaxis in 13 low-resource countries.

INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) provision is a priority intervention for high HIV prevalence settings and populations at substantial risk of HIV acquisition. This mathematical modelling analysis estimated the impact, cost and cost-effectiveness of scaling up oral PrEP in 13 countries. METHODS: We projected the impact and cost-effectiveness of oral PrEP between 2018 and 2030 using a combination of the Incidence Patterns Model and the Goals model. We created four PrEP rollout scenarios involving three priority populations-female sex workers (FSWs), serodiscordant couples (SDCs) and adolescent girls and young women (AGYW)-both with and without geographic prioritization. We applied the model to 13 countries (Eswatini, Ethiopia, Haiti, Kenya, Lesotho, Mozambique, Namibia, Nigeria, Tanzania, Uganda, Zambia and Zimbabwe). The base case assumed achievement of the Joint United Nations Programme on HIV/AIDS 90-90-90 antiretroviral therapy targets, 90% male circumcision coverage by 2020 and 90% efficacy and adherence levels for oral PrEP. RESULTS: In the scenarios we examined, oral PrEP averted 3% to 8% of HIV infections across the 13 countries between 2018 and 2030. For all but three countries, more than 50% of the HIV infections averted by oral PrEP in the scenarios we examined could be obtained by rollout to FSWs and SDCs alone. For several countries, expanding oral PrEP to include medium-risk AGYW in all regions greatly increased the impact. The efficiency and impact benefits of geographic prioritization of rollout to AGYW varied across countries. Variations in cost-effectiveness across countries reflected differences in HIV incidence and expected variations in unit cost. For most countries, rolling out oral PrEP to FSWs, SDCs and geographically prioritized AGYW was not projected to have a substantial impact on the supply chain for antiretroviral drugs. CONCLUSIONS: These modelling results can inform prioritization, target-setting and other decisions related to oral PrEP scale-up within combination prevention programmes. We caution against extensive use given limitations in cost data and implementation approaches. This analysis highlights some of the immediate challenges facing countries-for example, trade-offs between overall impact and cost-effectiveness-and emphasizes the need to improve data availability and risk assessment tools to help countries make informed decisions.

Age targeting and scale-up of voluntary medical male circumcision in Mozambique.

BACKGROUND: The voluntary medical male circumcision (VMMC) program in Mozambique aimed to increase male circumcision (MC) coverage to 80 percent among males ages 10 to 49 by 2018. Given the difficulty in attracting adult men over age 20 for circumcision, Mozambique became interested in assessing its age-targeting strategy and progress at the provincial level to inform program planning. METHODS: We examined the impact and cost-effectiveness of circumcising different age groups of men using the Decision Makers' Program Planning Toolkit, Version 2.1 (DMPPT 2). We also applied the model to assess the scale-up efforts through the end of September 2017 and project their impact on HIV incidence through 2030. The DMPPT 2 is a compartmental Excel-based model that analyzes the effects of age at circumcision on program impact and cost-effectiveness. The model tracks changes in age-specific MC coverage due to VMMC program circumcisions. Baseline MC prevalence was based on data from the 2011 Demographic and Health Survey. The DMPPT 2 was populated with HIV incidence projections from Spectrum/Goals under an assumption that Mozambique would reach its national targets for HIV treatment and prevention by 2022. RESULTS: We estimate the VMMC program increased MC coverage among males ages 10 to 49 from 27 percent in 2009 to 48 percent by end of September 2017. Coverage increased primarily in males ages 10 to 29. VMMCs conducted in the national program through the end of September 2017 are projected to avert 67,076 HIV infections from 2010 to 2030. Scaling up circumcisions in males ages 20 to 29 will have the most immediate impact on HIV incidence, while the greatest impact over a 15-year period is obtained by circumcising males ages 15 to 24 in the majority of priority provinces. Circumcising 80 percent of males ages 10 to 29 can achieve 77 percent of the impact through 2030 compared with circumcising 80 percent of males ages 10 to 49. CONCLUSION: The VMMC program in Mozambique has made great strides in increasing MC coverage, particularly for males ages 10 to 29. Scaling up and maintaining MC coverage in this age group offers an attainable and cost-effective target for VMMC in Mozambique.

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.