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Safety differences between tenofovir alafenamide/emtricitabine (TAF) and tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)-formulated pre-exposure prophylaxis (PrEP) appear to have little clinical significance for most PrEP users. Furthermore, generic TDF-formulated PrEP is projected to decrease the price of PrEP. Thus, efforts to shift PrEP users to TAF-formulated PrEP should be considered in light of their potential to undermine efforts to scale-up PrEP nationally. Data are taken from Together 5,000, a US national cohort study predominantly composed of cisgender gay and bisexual men. In 2019–2020, 5034 participants completed their 24-month assessment, which measured whether participants were switching from TDF (Truvada) to TAF (Descovy) for PrEP, and why. Of those reporting PrEP-use (n = 1009), 277 reported using Descovy for PrEP, and 223 provided a reason for switching to Descovy. A content analysis was used to code participant's reasons for switching. Over half (56%) of participants reported that their doctor recommended switching to Descovy. Without mentioning a provider recommendation, 32% of participants reported that perceived improved safety of Descovy, compared with Truvada, motivated their decision to change their prescription. Other factors cited included the smaller size of the pill and "newness" of Descovy. Further, several participants mentioned negative advertising about Truvada as rationale for switching. Although scientific consensus supports the safety of both TDF/FTC and TAF, our results suggest that current messaging through physicians and other sources have emphasized superior safety of TAF—implying that TDF/FTC may not be safe in the long term. Efforts to shift users onto TAF may undermine public perception of TDF-formulated PrEP. [ABSTRACT FROM AUTHOR]