INTRODUCTION: Eswatini achieved a 44% decrease in new HIV infections from 2014 to 2019 through substantial scale-up of testing and treatment. However, it still has one of the highest rates of HIV incidence in the world, with 14 infections per 1,000 adults 15-49 years estimated for 2017. The Government of Eswatini has called for an 85% reduction in new infections by 2023 over 2017 levels. To make further progress towards this target and to achieve maximum health gains, this study aims to model optimized investments of available HIV resources. METHODS: The Optima HIV model was applied to estimate the impact of efficiency strategies to accelerate prevention of HIV infections and HIV-related deaths. We estimated the number of infections and deaths that could be prevented by optimizing HIV investments. We optimize across HIV programs, then across service delivery modalities for voluntary medical male circumcision (VMMC), HIV testing, and antiretroviral refill, as well as switching to a lower cost antiretroviral regimen. FINDINGS: Under an optimized budget, prioritising HIV testing for the general population followed by key preventative interventions may result in approximately 1,000 more new infections (2% more) being averted by 2023. More infections could be averted with further optimization between service delivery modalities across the HIV cascade. Scaling-up index and self-testing could lead to 100,000 more people getting tested for HIV (25% more tests) with the same budget. By prioritizing Fast-Track, community-based, and facility-based antiretroviral refill options, an estimated 30,000 more people could receive treatment, 17% more than baseline or US$5.5 million could be saved, 4% of the total budget. Finally, switching non-pregnant HIV-positive adults to a Dolutegravir-based antiretroviral therapy regimen and concentrating delivery of VMMC to existing fixed facilities over mobile clinics, US$4.5 million (7% of total budget) and US$6.6 million (10% of total budget) could be saved, respectively. SIGNIFICANCE: With a relatively short five-year timeframe, even under a substantially increased and optimized budget, Eswatini is unlikely to reach their ambitious national prevention target by 2023. However, by optimizing investment of the same budget towards highly cost-effective VMMC, testing, and treatment modalities, further reductions in HIV incidence and cost savings could be realized.
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