The persistent challenge of HIV prevention may be shifting with the emergence of extended-duration prophylactic options that address the fundamental barriers limiting current prevention strategies. Traditional daily oral medications face significant adherence challenges, particularly among young women in high-burden regions where consistent pill-taking proves difficult to maintain over time. Lenacapavir represents a novel approach to pre-exposure prophylaxis, functioning as a capsid inhibitor that interferes with HIV replication through multiple mechanisms. After an initial oral loading dose, a single subcutaneous injection provides six months of protective coverage against HIV acquisition. This twice-yearly dosing schedule could dramatically reduce the adherence burden that undermines existing prevention efforts. The Cochrane systematic review protocol establishes the framework for evaluating this long-acting injectable against current standard options including daily oral combinations and three-monthly cabotegravir injections. While promising in concept, several critical factors will determine lenacapavir's real-world impact. The drug's effectiveness profile, safety considerations during extended exposure periods, and practical implementation challenges in resource-limited settings remain key evaluation points. Cost and healthcare infrastructure requirements for bi-annual injection programs could significantly influence accessibility. The review's focus on randomized controlled trial evidence will provide essential data, though longer-term population-level studies will ultimately determine whether this approach can meaningfully reduce global HIV incidence rates, particularly among the young women who bear disproportionate infection burdens.