OBJECTIVES: To assess the potential trade-offs between aggressive screening (“testing”) of the human immunodeficiency virus (HIV), early initiation of treatment (“test-and-treat”) with antiretroviral therapy (ART), and pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) in Los Angeles County (LAC). METHODS: A compartmental mathematical model is developed to simulate HIV incidence among 15-65 year old MSMs of LAC over a twenty-year period, and estimate the cost and effectiveness of various HIV interventions using a societal perspective and a lifetime horizon. Annual LAC MSM population data (2000-2010) are estimated from the LAC HIV Surveillance Reports and the RAND California Population and Demographics database. The model input parameter values are derived from the published clinical literature and the Federal Supply and IMS Fee Schedules. For each intervention, we estimate the number of new HIV infections averted, the discounted costs and quality-adjusted life years (QALYs), and the incremental cost per infection averted and cost-effectiveness ratios. Bootstrapping and probabilistic sensitivity analyses are conducted to assess the robustness of the estimates.  RESULTS: Our preliminary results show that relative to the status quo policy, and at the current US willingness to pay threshold of $100,000/QALY saved, both the PrEP, “testing” and “test-and-treat” strategies are cost-effective ($86,194; $44,746 and $94,520 per QALY saved, respectively). These results are imputable to the preventive and survival benefits of PrEP, knowledge of infection status, and early treatment. The relative effectiveness of PrEP is sensitive to PrEP and ART adherence and coverage rates. All cost-effectiveness profiles improve with ART price reductions following patent expiration. CONCLUSIONS: PrEP, “testing” and “test-and-treat” offer cost-effective alternatives to the status-quo policy. The success of the PrEP and “test-and-treat” strategies remains particularly contingent on the uptake rate and adherence to treatment. The lack of evidence on adherence behaviors towards PrEP thus warrants further studies that mimic real-world adherence patterns.