Objective: The fixed dose combination (FDC) of tenofovir disoproxil (TD) fumarate/emtricitabine (FTC) has been the most widely used backbone treatment for HIV until recently. In 2016, tenofovir alafenamide (TAF)/FTC became available as FDC, which promises superior renal and bone safety. However, in November 2016, the German Federal Joint Committee concluded that there is no additional benefit to the use of TAF versus TD fumarate. The decision of choosing TD or TAF in FDC with FTC is of economic impact as cost-saving generics (Gx-TD/FTC) became available in Germany in August 2017. Methods:A budget impact analysis (BIA) was conducted to estimate the impact of Gx-TD/FTC on the German healthcare system for 5-years. The BIA compared a theoretical setting with and without introduction of Gx-TD/FTC; calculating the respective costs for antiretroviral treatment, monitoring, and adverse event management.Results: Based on the model assumptions, low and high values of year-wise savings with Gx-TD/FTC throughout 5 years were estimated. The scenario of Gx-TD/FTC use growing to 35% by year 5, deemed the most realistic scenario(switch from TDF/FTC to Gx-TD/FTC only), would result in a saving of €22.6 million in first year and a maximum saving of €31.8 million by second year. In a maximum patient share scenario (80%) for Gx-TD/FTC which includes switch from branded TD fumarate/FTC and TAF/FTC, savings increased from €22.6 million annually to a maximum of €62.1 million. Conclusion:The estimated savings are based on a conservative approach and will be higher with increasing generic price rebates. Additionally, this analysis makes cautious assumptions in favor of patient safety and care pathways. This analysis highlights the potential for substantial and sustainable cost savings by the use of Gx-TD/FTC for the German healthcare system which is most pronounced when patients from branded TD fumarate/FTC and TAF/ FTC are switched to this generic treatment.