OBJECTIVES: Single tablet regimens like elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) for the treatment of HIV infection are associated with improved medication adherence, better virologic suppression, lower hospitalization rates, and lower healthcare costs. The objective of this study was to estimate the budget impact to a US healthcare plan of the use of EVG/COBI/FTC/TDF  in adults with HIV who are treatment-naïve or currently on treatment with no resistance to the components of EVG/COBI/FTC/TDF. METHODS: The model estimates total direct healthcare costs associated with HIV management before and after the introduction of EVG/COBI/FTC/TDF.  HIV epidemiology, hospitalization rates, and adverse event incidence and their associated costs were calculated using results of published studies or publically available sources. Regimen utilization was obtained from recent chart audit analysis and EVG/COBI/FTC/TDF market share was projected to come from protease inhibitor (PI)-based regimens in relative proportion to each regimen’s market share. The budget impact was calculated annually and cumulatively over a 3-year period without discounting, following standard methodology for budget impact analyses. RESULTS: For a hypothetical healthcare plan with 1 million members, the model estimated 450 HIV-positive members currently on treatment and 72 HIV-positive members initiating HIV therapy each year. Over a 3-year period, the introduction of EVG/COBI/FTC/TDF was expected to result in greater use of single tablet regimens and lower use of more expensive PI-based regimens, yielding lower pharmacy costs ($226,194, 0.5% lower), fewer hospitalizations (1.1% fewer), and lower hospitalization costs ($31,288, 1.1% lower) versus scenario without EVG/COBI/FTC/TDF. Total cost savings over 3 years were estimated at $240,375 (0.4% lower), equivalent to a reduction in per-member-per-month (PMPM) costs from $1.61 to $1.60. PMPM results were insensitive to changes in parameters.  CONCLUSIONS: The introduction of EVG/COBI/FTC/TDF is expected to result in fewer hospitalizations with a negligible impact on pharmacy and total costs over a 3-year period for a US healthcare plan.