Background: New York City (NYC) remains an epicenter of the HIV epidemic in the United States. Given the variety of evidence-based HIV prevention strategies available and the significant resources required to implement each of them, comparative studies are needed to identify how to maximize the number of HIV cases prevented most economically.

Methods: A new model of HIV disease transmission was developed integrating information from a previously validated micro-simulation HIV disease progression model. Specification and parameterization of the model and its inputs, including the intervention portfolio, intervention effects and costs were conducted through a collaborative process between the academic modeling team and the NYC Department of Health and Mental Hygiene. The model projects the impact of different prevention strategies, or portfolios of prevention strategies, on the HIV epidemic in NYC.

Results: Ten unique interventions were able to provide a prevention benefit at an annual program cost of less than$360,000, the threshold for consideration as a cost-saving intervention (because of offsets by future HIV treatment costs averted). An optimized portfolio of these specific interventions could result in up to a 34% reduction in new HIV infections over the next 20 years. The cost-per-infection averted of the portfolio was estimated to be $106,378; the total cost was in excess of $2 billion (over the 20 year period, or approximately $100 million per year, on average). The cost-savings of prevented infections was estimated at more than $5 billion (or approximately $250 million per year, on average).

Conclusions: Optimal implementation of a portfolio of evidence-based interventions can have a substantial, favorable impact on the ongoing HIV epidemic in NYC and provide future cost-saving despite significant initial costs.