ABSTRACT The Ending the HIV Epidemic (EHE) Initiative boldly aims to reduce HIV incidence in high burden areas by 90% by 2030, yet challenges remain in measuring incidence to identify priority populations and knowing how to best allocate local resources. To date, HIV molecular surveillance-based interventions have not been linked to a reduction in HIV incidence. That is (with rare exception), public health efforts directed to individuals associated with rapidly growing HIV transmission clusters have not been shown to reduce the number of new HIV infections or the proportion of people virally suppressed in the regions or groups where these services were delivered. There are no existing resource allocation models that are informed by local molecular and HIV program data to determine how to best allocate resources relevant to EHE targets. The “Los Angeles County ASsessment of Phylodynamics to Improve Resource Equity (LAC ASPIRE)” team will use i) advanced phylodynamic approaches and prospective measures of incidence to identify populations with the highest transmission rates in Los Angeles County (LAC) and ii) economic modeling to optimize allocation of public health program resources to achieve EHE and other stakeholder targets. The ASPIRE team is a partnership between investigators at several academic universities and the LAC Division of HIV and STD Programs (DHSP). Analyses will use coded and de-identified HIV surveillance data and program data provided by the LAC DHSP. The proposed study will identify LAC populations with the highest transmission rates and denote as priority populations. We will use economic modeling to develop strategies that optimize the allocation of prevention resources to i) reduce HIV incidence, ii) improve HIV-related health outcomes, and iii) improve equity across populations. We will engage stakeholders—defined as 1) LAC DHSP personnel, 2) those directly or indirectly involved in administering HIV Programs in LAC, and 3) persons with HIV (PWH) and other key affected populations—to provide guidance on population and resource prioritization strategies that are both regionally acceptable and most likely to achieve EHE targets. The overall study objective is to develop a process to guide decision-making related to allocation of HIV program resources by public health departments informed by regional program and transmission data. Project specific aims include: Aim 1 (IDENTIFY). Identify populations that are the highest priority for HIV prevention efforts (these data will inform the epidemic model used in Aim 2); Aim 2 (ALLOCATE). Develop a user-friendly dynamic transmission model that will project the impact of alternative strategies for the optimal allocation of resources to LAC HIV prevention programs (these data will project health outcomes and cost-effectiveness); and Aim 3 (ENGAGE). Engage key stakeholders to develop a process to guide project outcomes and build capacity at the LAC Health Department for data analysis th...