HIV infects more than a million people every year worldwide. While decades of research have led to effective treatments and pre-exposure prophylactic (PrEP) drugs that have dramatically reduced the impact of HIV/AIDS epidemic, completely wiping the virus out has remained out of reach. Lenacapavir, a new twice-yearly PrEP injection, may be the solution. Two clinical trials this year showed the drug can offer near complete protection from HIV infection, and the long-lasting effects mean daily pills could be a thing of the past, as long as it is accessible to populations who need it most. Science journalist Jon Cohen, physician-scientist Linda-Gail Bekker, and biochemist Wesley Sundquist describe the history of HIV/AIDS prevention and the unique mechanism that led lenacapavir to be named the 2024 Breakthrough of the Year. Read more about the Breakthrough of the Year: https://www.science.org/boty2024