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BACKGROUND: Estimated global new HIV infections among people who inject drugs (PWID) remained stable over the 2010-2015 period and the target of a 50% reduction over this period was missed. To achieve the 2020 UNAIDS target of reducing adult HIV infections by 75% compared to 2010, accelerated action in scaling up HIV programs for PWID is required. In a context of diminishing external support to HIV programs in countries where most HIV-affected PWID live, it is essential that available resources are allocated and used as efficiently as possible. METHODS: Allocative and implementation efficiency analysis methods were applied. Optima, a dynamic, population-based HIV model with an integrated program and economic analysis framework was applied in eight countries in Eastern Europe and Central Asia (EECA). Mathematical analyses established optimized allocations of resources. An implementation efficiency analysis focused on examining technical efficiency, unit costs, and heterogeneity of service delivery models and practices. RESULTS: Findings from the latest reported data revealed that countries allocated between 4% (Bulgaria) and 40% (Georgia) of total HIV resources to programs targeting PWID - with a median of 13% for the eight countries. When distributing the same amount of HIV funding optimally, between 9% and 25% of available HIV resources would be allocated to PWID programs with a median allocation of 16% and, in addition, antiretroviral therapy would be scaled up including for PWID. As a result of optimized allocations, new HIV infections are projected to decline by 3-28% and AIDS-related deaths by 7-53% in the eight countries. Implementation efficiencies identified involve potential reductions in drug procurement costs, service delivery models, and practices and scale of service delivery influencing cost and outcome. A high level of implementation efficiency was associated with high volumes of PWID clients accessing a drug harm reduction facility. CONCLUSION: A combination of optimized allocation of resources, improved implementation efficiency and increased investment of non-HIV resources is required to enhance coverage and improve outcomes of programs for PWID. Increasing efficiency of HIV programs for PWID is a key step towards avoiding implicit rationing and ensuring transparent allocation of resources where and how they would have the largest impact on the health of PWID, and thereby ensuring that funding spent on PWID becomes a global best buy in public health.