Lenacapavir: A Twice-Yearly Injectable for HIV Preexposure Prophylaxis.

OBJECTIVE

To review the efficacy and safety of lenacapavir for the prevention of HIV-1 infection.

DATA SOURCES: Clinical trials and review articles were obtained through August 2025 using search terms lenacapavir, GS-CA1, GS-6207, capsid inhibitor, preexposure prophylaxis, and PrEP.

STUDY SELECTION AND DATA EXTRACTION: All relevant articles, trials, and abstracts in the English language were included.

DATA SYNTHESIS: Lenacapavir uses a novel mechanism for HIV prevention administered through subcutaneous injection. In a counterfactual design, lenacapavir arms demonstrated superior efficacy for prevention against a background HIV incidence rate across a variety of populations and gender identities. Adverse events commonly reported include injection-site reactions, which may include nodules, pain, or swelling at the injection site.Relevance to Patient Care and Clinical Practice in Comparison to Existing Drugs:The extended dosing frequency of lenacapavir may uniquely serve patients at risk of HIV acquisition who are unable or unwilling to take oral prevention medications. The mechanism of action for lenacapavir is not duplicative of other medications used in first-line antiretroviral regimens and thus may not risk resistance to regularly used classes if resistance occurs. Lenacapavir is a moderate cytochrome P450 inhibitor and thus may have interactions with other medications; however, neither renal nor hepatic dose adjustments are required.

CONCLUSIONS

Lenacapavir provides a long-acting injectable option for people seeking a pharmacologic prevention agent against HIV-1. Despite injection-site reactions being relatively common, these did not present a barrier to treatment continuation among trial participants.