Apretude (cabotegravir) may cause fewer injection-related side effects than Yeztugo (lenacapavir) for pre-exposure prophylaxis (PrEP), but it needs to be taken more often. Apretude, from ViiV Healthcare, is administered as a single intra-muscular injection every other month, while Yeztugo, from Gilead Sciences, is administered as two subcutaneous injections every six months. Yeztugo forms a depot under the skin that can sometimes be felt as a hard nodule. In the Phase I CLARITY trial, sponsored by ViiV, 63 people were randomized to receive a single dose of Apretude or Yeztugo, followed by the other 15 days later. About 80% reported pain after both injections, but other reactions were more common with Yeztugo. Most were mild or moderate. After receiving one dose of both, 69% found Apretude injections very or totally acceptable, compared with 48% for Yeztugo. Most (90%) said they preferred Apretude, while 10% preferred Yeztugo. These findings suggest that PrEP users may face a trade-off between more tolerable injections and less frequent dosing.