A huge Phase III trial of a long-acting injectable form of the experimental antiretroviral cabotegravir for use as pre-exposure prophylaxis (PrEP) against HIV has begun. The randomized, double-blind HPTN 083 trial will enroll 4,500 HIV-negative transgender women and cisgender men who have sex with men. The trial, to be conducted at 45 sites in eight countries in the Americas, Asia and Africa, will determine whether long-acting cabotegravir injected every eight weeks protects against HIV as well as daily oral Truvada (tenofovir disoproxil fumarate/emtricitabine) among the high-risk participants. The study members will be randomly assigned to receive one drug or the other and will remain in the trial for an average of four and a half years. Results are expected in 2021. Another study, HPTN 084, will test the safety and efficacy of long-acting injectable cabotegravir as PrEP among young women in sub-Saharan Africa starting this year.