Emerging concepts in HIV pre-exposure prophylaxis: focus on twice-yearly lenacapavir

The persistent global burden of HIV and the need for more flexible, durable prevention strategies have accelerated the development of long-acting pre-exposure prophylaxis (PrEP) options. Lenacapavir (LEN), a first-in-class capsid inhibitor, is approved as a twice-yearly subcutaneous injection for HIV prevention and represents a major advance beyond oral injectable PrEP regimens administered daily or every 2 months. Data from phase III trials demonstrate high efficacy, sustained drug levels and strong adherence potential, positioning LEN as a transformative option for individuals seeking long-acting protection. Its unique mechanism of action and extended dosing interval can address key barriers to PrEP uptake and persistence, particularly amongst populations disproportionately at risk for HIV. LEN may play a central role in expanding choice and improving the real-world effectiveness of PrEP. Ongoing considerations include implementation logistics, equitable access, potential drug resistance and integration into existing prevention frameworks. Twice-yearly LEN is a critical addition to the evolution of HIV prevention strategies.