Background Single tablet antiretroviral regimens (STR) offer one-pill, once-a-day dosing for people living with HIV. In commercially insured populations under 50 years of age, these formulations have been associated with better adherence and lower healthcare resource utilization and costs compared to multi-tablet regimens (MTR). The objectives of this dissertation were to detail patterns of STR and MTR use and the associated healthcare utilization, incremental costs, and overall budget impact among Medicare beneficiaries living with HIV. We relied on Andersen’s Behavioral Model, Generalized Estimating Equations (GEE), instrumental variable regression, and budget impact modeling to answer these questions. Methods Using a 5% random sample of Medicare Fee-for-Service beneficiaries from the Chronic Conditions Data Warehouse (CCW) we identified Medicare beneficiaries living with HIV from January 1, 2014 through December 31, 2019. We used generalized estimating equation to estimate trends in antiretroviral and other healthcare resource utilization. We estimated 1-year incremental total direct medical costs with an instrumental variable approach via two-stage least squares regression. We utilized these estimates of utilization and costs to build a five-year budget impact model. Results Among 8,316 Medicare beneficiaries contributing 282,258 person-months of observation, STR receipt was 24% more likely in 2019 (57%) than it was in 2014 (27%), and integrase-based regimens were predominant among both STR (80%) and MTR (74%) by 2019. Among 7,044 beneficiaries who initiated a new ART regimen, the instrumented STR variable was associated with statistically significant lower 1-year incremental total direct medical costs compared to MTR (-$13,487.70, (95% Confidence Interval: -$16,750.77 to -$10.224.63), p<.001). Our budget impact model predicted $1.8 billion in additional costs in year 5 under a scenario where current trends in ART utilization and list prices continue compared to a scenario where they remain at 2019 levels. The excess costs were driven by $2.3 billion in greater ART spending among the 147,953 beneficiaries living with HIV despite reductions in all other healthcare resource utilization categories and related savings. Conclusion These findings demonstrate the adoption and predominance of STR and integrase-based regimens among Medicare beneficiaries living with HIV. STRs were associated with significantly lower 1-year total direct medical costs compared to MTR among an understudied population. This study improves upon prior study designs and demonstrates the usefulness of prescriber preference IVs. However, the magnitude of the reduction in HcRU associated with STR may not be adequate enough to justify increases in ART costs as was observed during the study period. Though still small in number, the costs of caring for people living with HIV in Medicare will likely continue to grow as a proportion of total spending and will be markedly impacted by any policies aimed at controlling expenditures on prescription drugs.